108,99 €
Mehr erfahren.
- Herausgeber: John Wiley & Sons
- Kategorie: Wissenschaft und neue Technologien
- Sprache: Englisch
Discover the biology, biochemistry, and medical aspects of lipoproteins in this comprehensive overview of its historic and contemporary development
The fatty substance known as cholesterol is found in every cell of the human body and carries out several important functions. It is transported through the bloodstream as a part of particles called lipoproteins, which are divided into classes including low-density lipoprotein (LDL) and high-density lipoprotein (HDL). Distinguishing between these two classes, along with the ‘remnant cholesterol’ particles that have recently been associated with heightened risk of heart disease and stroke, is a crucial part of managing health and developing novel pharmaceuticals.
Cholesterol, Lipoproteins, and Cardiovascular Health offers a thorough and rigorous overview of these particles, their properties, and their methods of categorization. Surveying both the characteristics of lipoproteins and their interactions with diet, lifestyle, therapeutics, and general health, it’s an indispensable guide to these particles that can literally mean the difference between life and death. Cutting-edge and grounded in the latest research, it’s a one-stop shop for understanding blood plasma lipoproteins in all their major forms.
Cholesterol, Lipoproteins, and Cardiovascular Health readers will also find:
- Detailed discussion of topics including basic lipoprotein biochemistry, targeted therapeutics and drug development, and many more
- Easily readable overview of the current state of research into lipoproteins and their likely future applications
- Rich illustrative material enhanced by a graphical abstract at the beginning of each section offering a summary of crucial content
Cholesterol, Lipoproteins, and Cardiovascular Health is suited for professionals, clinicians, and readers looking for a comprehensive overview of all aspects of plasma lipoproteins and their role in heart disease and stroke.
Das E-Book können Sie in Legimi-Apps oder einer beliebigen App lesen, die das folgende Format unterstützen:
Veröffentlichungsjahr: 2024
Ähnliche
Table of Contents
Cover
Table of Contents
Title Page
Copyright
Brief History of Lipoproteins
Cholesterol and LDL
HDL
Remnant Cholesterol
Preface
Acknowledgments
Abbreviations
Prologue
Setting: Realms of Molecules, Cells and Diseases
1 Covert World of Molecules
Cholesterol
Lipids
Proteins
2 Enigmatic World of Cells and Organs
Cells
Organs
3 Shadowy World of Diseases
Atherosclerosis
Cardiovascular Disease
Further Reading
Characters: Lipoproteins of Human Blood
Test Your Knowledge
Answers
Main Character One: LDL, Carrier of “Bad” Cholesterol
4 LDL – Why It Is Important
Epidemiology
Genetics
5 LDL – What It Is
Proteins
Lipids
Heterogeneity
6 LDL – Where It Comes From
Lipolysis
Lipid Transfer
7 LDL – What It Does
Supply of Cholesterol
Removal of Cholesterol
8 LDL – How It Stops Working
Causes
Consequences
9 LDL – What to Do to Correct It
Lifestyle
Therapy
Test Your Knowledge
Answers
Further Reading
Main Character Two: HDL, Carrier of “Good” Cholesterol
10 HDL – Why It Is Important
11 HDL – What It Is
Proteins
Lipids
Heterogeneity
Structure
12 HDL – Where It Comes From
Transporters
Enzymes
Lipid Transfer Proteins
Receptors
Removal
13 HDL – What It Does
Removal of Cholesterol
Inhibition of Oxidation
Reduction of Inflammation
Protection from Cell Death
Defense Against Infection
Relaxation of Vessels
Attenuation in Clotting
Improvement of Sugar Processing
14 HDL – How It Stops Working
Causes
Consequences
15 HDL – What To Do To Correct It
Lifestyle
Therapy
Test Your Knowledge
Answers
Further Reading
Main Character Three: Triglyceride-Rich Lipoproteins, Carriers of Remnant Cholesterol
16 Remnant Cholesterol – Why It Is Important
Epidemiology
Genetics
17 Remnant Cholesterol – What It Is
Chylomicrons
VLDL
IDL and Other Remnants
Proteins
Lipids
Heterogeneity
18 Remnant Cholesterol – Where It Comes From
Production of Triglyceride-Rich Lipoproteins
19 Remnant Cholesterol – What It Does
Lipolysis as a Source of Energy
Removal
20 Remnant Cholesterol – How It Stops Working
Causes
Consequences
21 Remnant Cholesterol – What to Do to Correct It
Lifestyle
Therapy
Test Your Knowledge
Answers
Further Reading
Epilogue
Glossary
Index
End User License Agreement
Guide
Cover
Table of Contents
Title Page
Copyright
Brief History of Lipoproteins
Preface
Acknowledgments
Abbreviations
Prologue
Begin Reading
Epilogue
Glossary
Index
End User License Agreement
Pages
iii
iv
xi
xii
xiii
xiv
xv
xvii
xviii
xix
xx
xxi
xxii
1
3
4
5
6
7
8
9
10
11
12
13
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
71
72
73
74
75
76
77
78
79
80
81
82
83
84
85
86
87
88
89
90
91
92
93
94
95
96
97
98
99
100
101
102
103
105
106
107
108
109
110
111
112
113
114
115
116
117
118
119
120
121
122
123
124
125
126
127
128
129
130
131
132
133
134
135
136
137
138
139
140
141
142
143
144
145
146
147
148
149
150
151
152
153
154
155
157
158
159
160
161
162
163
164
165
166
167
168
169
171
172
173
174
175
176
177
178
179
180
181
182
183
184
185
186
187
188
189
190
191
192
193
195
196
197
198
199
200
201
202
203
204
205
206
207
208
209
210
211
212
213
214
215
216
217
218
219
220
221
222
223
224
225
226
227
228
229
230
231
233
234
235
236
237
238
239
240
241
242
243
244
245
246
247
248
249
250
251
252
253
254
255
256
257
259
261
262
263
264
265
266
267
268
269
270
271
272
273
274
275
276
277
278
279
280
281
282
283
284
285
286
287
288
289
290
291
292
293
294
295
296
297
298
299
300
301
302
303
304
305
306
307
308
309
310
311
312
313
314
315
316
317
318
319
320
321
322
323
325
326
327
328
329
330
331
332
333
334
335
336
337
338
339
340
341
342
343
344
345
346
347
348
349
350
351
352
353
354
355
356
357
358
359
360
361
362
Cholesterol, Lipoproteins, and Cardiovascular Health
Separating the Good (HDL), the Bad (LDL), and the Remnant
Anatol Kontush
Sorbonne University
Paris, France
Copyright © 2025 by John Wiley & Sons, Inc. All rights reserved, including rights for text and data mining and training of artificial intelligence technologies or similar technologies.
Published by John Wiley & Sons, Inc., Hoboken, New Jersey.Published simultaneously in Canada.
No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, scanning, or otherwise, except as permitted under Section 107 or 108 of the 1976 United States Copyright Act, without either the prior written permission of the Publisher, or authorization through payment of the appropriate per-copy fee to the Copyright Clearance Center, Inc., 222 Rosewood Drive, Danvers, MA 01923, (978) 750-8400, fax (978) 750-4470, or on the web at www.copyright.com. Requests to the Publisher for permission should be addressed to the Permissions Department, John Wiley & Sons, Inc., 111 River Street, Hoboken, NJ 07030, (201) 748-6011, fax (201) 748-6008, or online at http://www.wiley.com/go/permission.
Trademarks: Wiley and the Wiley logo are trademarks or registered trademarks of John Wiley & Sons, Inc. and/or its affiliates in the United States and other countries and may not be used without written permission. All other trademarks are the property of their respective owners. John Wiley & Sons, Inc. is not associated with any product or vendor mentioned in this book.
Limit of Liability/Disclaimer of Warranty: While the publisher and author have used their best efforts in preparing this book, they make no representations or warranties with respect to the accuracy or completeness of the contents of this book and specifically disclaim any implied warranties of merchantability or fitness for a particular purpose. No warranty may be created or extended by sales representatives or written sales materials. The advice and strategies contained herein may not be suitable for your situation. You should consult with a professional where appropriate. Further, readers should be aware that websites listed in this work may have changed or disappeared between when this work was written and when it is read. Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages.
For general information on our other products and services or for technical support, please contact our Customer Care Department within the United States at (800) 762-2974, outside the United States at (317) 572-3993 or fax (317) 572-4002.
Wiley also publishes its books in a variety of electronic formats. Some content that appears in print may not be available in electronic formats. For more information about Wiley products, visit our web site at www.wiley.com.
Library of Congress Cataloging-in-Publication Data:
Names: Kontush, Anatol, author.
Title: Cholesterol, lipoproteins, and cardiovascular health : separating the good (HDL), the bad (LDL), and the remnant / Anatol Kontush.
Description: Hoboken, New Jersey : Wiley, [2025] | Includes bibliographical references and index.
Identifiers: LCCN 2024022148 (print) | LCCN 2024022149 (ebook) | ISBN 9781394158379 (hardback) | ISBN 9781394158362 (adobe pdf) | ISBN 9781394158386 (epub)
Subjects: MESH: Cholesterol | Lipoproteins | Cardiovascular Diseases
Classification: LCC QP752.C5 (print) | LCC QP752.C5 (ebook) | NLM QU 95 | DDC 572/.5795–dc23/eng/20240625
LC record available at https://lccn.loc.gov/2024022148
LC ebook record available at https://lccn.loc.gov/2024022149
Cover Design: WileyCover Image: Courtesy of Anatol Kontush
Brief History of Lipoproteins
Cholesterol and LDL
Identification of cholesterol
Description of cholesterol-containing arterial lesions
Experimental induction of atherosclerosis
Isolation and purification of plasma lipoproteins
Separation of lipoproteins by ultracentrifugation
Plasma cholesterol and heart disease
Classification of dyslipidemias
Discovery of the LDL receptor
Discovery of the first statin
Reduction of heart disease by lowering blood cholesterol
HDL
Low HDL-cholesterol and heart disease
Apolipoprotein A-I Milano
ABC classification of apolipoproteins
Heterogeneity of HDL
Double belt model
Cholesterol esterification and reverse cholesterol transport
Cellular cholesterol transporters
The HDL hypothesis
Unexpected therapeutic failures
U-shaped epidemiology
Remnant Cholesterol
Discovery of chylomicrons
Discovery of triglyceride-rich lipoproteins
The concept of chylomicron remnants
Discovery of apolipoprotein E
Discovery of lipoprotein lipase
Links between triglyceride-rich lipoproteins and HDL
Atherogenicity of triglyceride-rich lipoproteins
Discovery of CETP
Discovery of fibrates
The response-to-retention hypothesis of atherosclerosis
Preface
Why add yet another book about cholesterol?
The answer is easy for someone who has worked on lipoproteins for over 30 years. There are many books about cholesterol but very few about lipoproteins.
You might be wondering what they are – and that’s the key point. Many people know about cholesterol, but not many know about lipoproteins. You can ask your doctor to check your good and bad cholesterol, but you might not realize that they are actually just different types of lipoproteins – the particles that carry cholesterol in your blood. Lipoproteins play a big role in heart disease and stroke, which together kill about a third of the world’s population. It has made over a billion since 1950, far surpassing all wars combined.
This book offers a comprehensive introduction to blood plasma lipoproteins for the public. These tiny particles play a crucial role in determining our life span and reside in the hidden world of the blood vessels. Plasma lipoproteins are divided into different classes, each with its own distinct universe of particles. Lipoproteins are responsible for transporting fats, also known as lipids, throughout the body. The lipids are central for providing energy and ensuring survival. However, when these particles are altered, they can become harmful, a common occurrence that we should be aware of.
A timeline highlighting significant milestones in our comprehension of cholesterol and lipoproteins.
The book is initially focused on two lipoproteins, commonly known as “bad” and “good” cholesterol. They are not. These complex particles contain many molecules, including cholesterol. They are essential for carrying lipids, and proteins play a major role in this. In this nanoworld we’ll meet other members from the lipoprotein family. This includes lipoproteins that are rich in triglycerides, which contain remnant cholesterol. Like other lipids in the body, cholesterol is also essential for life. It is the molecule, however, that damages the arteries, causes stroke and heart disease, and can create other problems.
We will explore the history of lipoproteins and cholesterol by examining the evolution of the science. The history of lipoproteins is filled with unexpected discoveries and unpredicted twists. These enigmatic realms took more than two centuries to unravel. Google Book Viewer says that the word “cholesterol,” which first appeared in books published at the end of the 19th century, gained popularity during the first half of the 20th century, and then became really popular after the link between cholesterol and heart diseases was discovered. The clinical role of cholesterol sparked a lot of interest. The development of a technique to isolate the two lipoproteins, low-density (LDL) and high-density (HDL), that transport the majority of cholesterol in the bloodstream, helped increase the popularity of this molecule. It’s no surprise that the popularity levels of these three terms are largely correlated.
The use of the terms “cholesterol,” “LDL,” and “HDL” has significantly risen over time.
Source: Google Books Ngram Viewer.
These studies began as basic research, with little or no relevance to medicine. Later, the discovery of the role played by cholesterol and lipoproteins on heart disease shifted the field into clinical science. We will be able to learn about the greatest achievements within their historical context. These studies covered a wide geographical area, from Europe to America and back again, Japan and other parts.
The geographical distribution of the milestones in the field of cholesterol and lipoproteins.
This book provides a comprehensive overview of lipoproteins, including their main classes and the latest biochemistry. It also includes clinical information as well as medical advice. We’ll learn why lipoproteins are important, how they function, what they do and why they exist. We’ll also see how they stop working and how to fix it with lifestyle and medical treatment. When reading, it is important to bear in mind that the author of this book is a researcher, not a physician.
Despite the challenges, lifestyle changes that correct lipoprotein processing remain the first medical option. The therapies are the last resort, but they are often necessary and can prolong and improve life. The development of new therapies is constant, and they make their way into the clinic. However, it’s not always easy to predict how and when they will work. After decades of hardwork, this field of biomedical science at the intersection of biochemistry and biology remains fascinating.
Acknowledgments
I want to express my deepest appreciation to M. John Chapman, who invited me to work on plasma lipoproteins and heart disease at his lab in Paris and supported me over long time. For more than 20 years, John’s expertise, guidance, finesse, and friendliness were the foundation of all my scientific studies and writings. I truly had the chance to join the excellent lab of John who introduced me to the world of international research and connected me with top scientists in the field.
I could not have undertaken this journey without Ulrike Beisiegel who led my work on lipoproteins at the University of Hamburg in Germany during the 1990s. Ulrike opened up the world of lipoproteins, atherosclerosis, and heart disease to me and continuously supported me and my family over these years without any doubts, providing me with the unique opportunity to work at her wonderful lab.
I am extremely grateful to all my colleagues from Paris and Hamburg whom I greatly enjoyed working with. My thanks primarily go to Christoph Hübner, Alfried Kohlschütter, Wilfried Weber, Barbara Finckh, Sandrine Chantepie, Marie Lhomme, Isabelle Guillas and Maryam Darabi, but equally to Juliana Bergmann, Nico Donarski, Helga Reschke, Jörg Heeren, Dieter Münch-Harrach, Andreas Niemeier, Alexander Mann, Annette Krapp, Susanne Ahle, Stefanie Koch, Sönke Arlt, Sven Schippling, Dave Evans, Dorte Wendt, Christine Runge, Jan Hinrich Bräsen, Carsten Buhmann, Hans-Jörg Stürenburg, Ulrike Mann, Stephanie Meyer, Barbara Karten, Torsten Spranger, Sirus Djahansouzi, Philippe Giral, Eric Frisdal, Maryse Guerin, Martine Moreau, Roberte Le Galleu, Françoise Berneau, Boris Hansel, Laurent Camont, Alexina Orsoni, Samir Saheb, Carolane Dauteuille, Sora Lecocq, Hala Hussein, Martine Couturier, Murielle Atassi, Paul Robillard, Farid Ichou, Alexandre Cukier, Emilie Tubeuf, Aurelie Canicio, Lucie Poupel, Clement Materne, Alain Carrié, Philippe Couvert, Olivier Bluteau, Thierry Huby, Emmanuel Gautier, Eric Bruckert, Dominique Bonnefont-Rousselot, André Grimaldi, Patrice Therond, Anne Négre-Salvayre, Robert Salvayre, Randa Bittar, Antonio Gallo, Maharajah Ponnaiah, Herve Durand, Sophie Galier and Martine Glorian for their kindness, patience, help, and advice. I am particularly thankful to Philippe Lesnik and Wilfried Le Goff for their continuous support and encouragement of my studies at Sorbonne University and Institut National de la Santé et de la Recherche Médicale (INSERM). I would like to recognize the important support continuously provided by Stéphane Hâtem, Director of the Research Unit 1166 and Head of the IHU ICAN in Paris. I would also like to extend my sincere thanks to all my graduate and doctoral students, postdoctoral researchers, engineers, and technicians whose brightness, enthusiasm, and hard work enriched my vision of the world of research. Many thanks also go out to all my colleagues and friends doing research worldwide in France, Germany, the USA, England, Australia, Canada, Mexico, Italy, the Netherlands, Austria, Sweden, Finland, Switzerland, Croatia, Greece, Brazil, Argentina, Russia, China, Iran, Lebanon, Israel, and other countries whom I relished working with over my career. I would like to acknowledge the generous support from Sorbonne University and INSERM which financed a large part of my research. I would be remiss in not mentioning the University of Odessa in the USSR where I received excellent training.
I am sincerely grateful to Elisa Campos for her outstanding PhD thesis on the history of lipoproteins which greatly aided my research into the past. I also want to thank Børge Nordestgaard for his excellent lectures which inspired the title and cover of this book.
I am truly thankful for the invaluable advice on this manuscript provided by my esteemed colleagues and friends, Philippe Giral and M. John Chapman.
I express my sincere gratitude to all the researchers acknowledged in the manuscript and extend my apologies to those whose contributions could not be cited due to space constraints.
Finally, I want to express my heartfelt thanks to my family. My dear parents, physicists Sergey and Svetlana, first sparked my interest in science. My loving and supportive Varya has always been there for me. My beloved children Michael, Anna and Konstantin have been a constant source of encouragement. My aunt Barbara and grandmother Irina were instrumental in helping me launch my career. My family’s unwavering belief in me kept me motivated and upbeat throughout the writing of this book. I also want to thank my childhood friends, who have continued to inspire me over the years.
Abbreviations
Abbreviations are common in every scientific field. While they are helpful for specialists, they can be overwhelming for newcomers. Whether they have a positive or negative impact, it’s impossible to understand scientific conversations without them. We will strive to minimize their use and only include essential ones.
Here they are:
4S:
Scandinavian Simvastatin Survival Study
ABC:
ATP binding cassette
ABCA1:
ATP-binding cassette transporter A1
ABCG1:
ATP-binding cassette transporter G1
ACC:
American College of Cardiology
ANGPTL:
angiopoietin-like protein
APO:
apolipoprotein
ATP:
adenosine triphosphate
BET:
bromodomains and extra-terminals
BMI:
body mass index
CETP:
cholesteryl ester transfer protein
GPIHBP1:
glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1
HDL:
high-density lipoprotein
HMG-CoA:
hydroxymethylglutaryl coenzyme A
IDL:
intermediate-density lipoprotein
LCAT:
lecithin-cholesterol acyltransferase
ILLUMINATE:
Investigation Of Lipid Level Management To Understand Its Impact In Atherosclerotic Events trial
INTERHEART:
Effect of Potentially Modifiable Risk Factors Associated with Myocardial Infarction study
LDL:
low-density lipoprotein
Lp(a):
lipoprotein (a)
LPL:
lipoprotein lipase
LPR:
LDL receptor-related protein
NADH:
nicotinamide adenine dinucleotide phosphate
mRNA:
messenger RNA
NIH:
National Institute(s) of Health
NMR:
nuclear magnetic resonance
OH:
hydroxyl
PAF-AH:
platelet activating factor-acetylhydrolase
PCSK9:
proprotein convertase subtilisin kexin type 9
PLTP:
phospholipid transport protein
PON:
paraoxonase
PPAR:
peroxisome proliferator-activated receptor
SAA:
serum amyloid A
Sf:
Svedberg flotation unit
SR-BI:
scavenger receptor class B type 1
VLDL:
very low-density lipoprotein
Prologue: The Story of Life and Death
This book isn’t just about cholesterol.
It’s primarily about the story of life and death, with cholesterol being just one piece of the larger picture.
This story takes place in the invisible realms of the body. This is a network of complex, intricate, invisible worlds. Each has its own complexity. These worlds are made up of visceral organs and functional systems. They also contain interconnected cells and countless molecules. In these worlds, we can find the cardiovascular system and arteries, livers, intestines, hepatocytes, macrophages, endothelial cells, platelets, cholesterol, and lipids. The story of this book is told in these invisible worlds.
This book is centered on cholesterol, which is known for its connection to heart disease. Other molecules, such as proteins and lipids, also play an important role. Hepatocytes, macrophages, endothelial cells, platelets, and other cells are the main players, while the primary affected organs are arteries and heart. These components are all vital to the cardiovascular system.
The book’s narrative will be set in these unseen worlds and encompass universal themes such as suffering, healing, mortality, and death. The story will progress as it explores the worlds of heart disease and atherosclerosis, each from a unique perspective. We will investigate the covert world of molecules, the enigmatic world of cells and organs as well as the shadowy world of diseases.
Our story takes place in this setting, where the characters are brought to life.
Like in any story, there are characters who steal the show and those who don’t. Lipoproteins are just one of the many residents in these invisible worlds. Two of them have gained international fame, as the “good” and “bad” cholesterol. The rising star of this family, however, is remnant cholesterol.
The three main characters in the story are sometimes referred to by the terms “good”, “bad” and “ugly”. These labels do not capture their complexity. Each character has both good and bad traits. This makes them more nuanced. The circumstances of each character influence their actions, and the ending of the story is determined by these factors. Each character will do anything to achieve their goals and influence the story in their favor, regardless of their circumstances.
As they navigate through the complex network of organs and cells, the characters interact with one another. They operate in different environments, such as intravascular, intracellular and extracellular.
This book introduces to a wide audience the main characters known as lipoproteins. They are critically important for the development of heart disease and other disorders. The book will show the characters as they move through the different worlds. The book starts by setting the scene, introducing characters, and then diving into the story.
Lipoproteins form the link between the invisible worlds of cholesterol, lipids, cells, organs, and atherosclerosis. They are a key component of this complex web, and weave a long and winding pathway that connects these worlds.
Setting: Realms of Molecules, Cells and Diseases
1Covert World of Molecules
Cholesterol
Why is cholesterol a problem? Why is this substance so vital? Has this always been the case?
There are both simple and complex answers to these questions. The simple answer is that cholesterol is believed to play a crucial role in determining our lifespan. In other words, cholesterol is thought to be central to the fundamental question of life and death, which is arguably the most important question known to humankind. We believe that cholesterol is responsible for heart disease – an illness that claims more lives than any other cause. This statement may seem paradoxical when we consider that cholesterol is actually an essential substance that the human body requires for good health. How can it be that a fundamental component of the body can become harmful and even life-threatening?
The liver, intestines, arteries, and heart (clockwise from the top left) are the primary organs involved in the processing of cholesterol (center) and its connection to heart disease. The hydrophilic OH group of cholesterol is in dark red.
Cholesterol, a type of fat, is necessary for the proper function of the body. There are biochemical pathways which aim to recycle and spare this compound.
Under normal conditions, it is a solid yellowish substance. Every cell in the body contains cholesterol. It is also an important component of lipoproteins. Animal cells produce cholesterol through a multistep complex process. By contrast, it is almost absent in bacteria.
The liver and intestines are the main sites of cholesterol production. The brain, the adrenal glands, and the reproductive organs are also sites where cholesterol is actively synthesized in humans. The brain contains a large amount of cholesterol, which accounts for about one-quarter of the total cholesterol in the human body.
Almost all cells in the body are capable of synthesizing cholesterol. Like other biological molecules, cholesterol also needs to be replaced and destroyed regularly. However, not all cells can do it. Only liver cells are able to degrade cholesterol in large quantities. Transport to the liver is necessary for continual cholesterol turnover within cells.
Cells cannot function properly without cholesterol and will die. In addition, cholesterol is used to make hormones, such as steroid hormones, stress hormones, vitamins, such as vitamin D, and bile acids that help digest food. Finally, cholesterol is important for fighting bacteria and infections.
Cholesterol is essential to separate cells from their surroundings. Cell membranes, thin structures that regulate cellular interactions with their environment, fulfill this function. Membranes are made of a material which cannot easily be destroyed by water. This kind of material is well known to everybody – it is fat. Cell membranes, which are mostly made of fat and protein, include a large amount of cholesterol.
The cholesterol in the body is a fat that is almost insoluble in water. It can also be mixed with other fats. These substances are known as lipophilic, from the Greek words “lipos,” meaning “fat” and “philia,” meaning “love.” Up to 30% of animal cell membranes are composed of cholesterol. The fatty myelin sheath that coats neuronal cells is about one-fifth cholesterol. Communications between neuronal cells critically depend on cholesterol.
Interesting Numbers
The average human body contains 35 grams (0.05%) of cholesterol, which is mostly found in the cell membranes. An average human synthesizes approximately 900 milligrams of cholesterol per day.
The cell membrane is composed of a bilayer made up of phospholipids and cholesterol. Cholesterol molecules are depicted in yellow, while phospholipids are represented in grey.
We all know that cholesterol can be both good and bad. These terms used by doctors around the world are familiar to us. The terms do not, however, precisely reflect the positive and negative effects of cholesterol on living organisms. As we shall see, they are derived from the measurements of cholesterol levels in blood plasma.
Interesting Numbers
In the United States, a typical daily cholesterol intake is around 300 milligrams.
All animal foods are cholesterol rich, as cholesterol is synthesized in animal cells. The amount of cholesterol in food varies greatly. Cholesterol is a major component of red meat, whole eggs, and egg yolks. In addition to liver, kidneys, giblets, and fish oil, butter also contains significant quantities of cholesterol. Not negligible amounts of cholesterol are also found in human breast milk.
Foods high in cholesterol: red meat, eggs, and butter.
Cholesterol molecule consists of four carbon rings, a hydrophobic side chain and a hydrophilic hydroxyl group OH. The molecule is rigid except for the side chain. The hydroxyl group interacts with water molecules surrounding the membrane, while the side chain is stuck in the cell membrane alongside the hydrophobic chains of phospholipids. This is how cholesterol interacts and works with other lipids to regulate fluidity in cell membranes and to maintain their integrity.
What It Is
Hydrophobic is derived from the Greek words for water (hydros) and fear (phobos). It means having little or no affinity for water.
Hydrophilic is derived from the Greek for water (hydros) and love (philia). It means having an affinity for water and being capable of interacting with it.
Hydrophilic substances mix easily with water, while hydrophobic substances repel it strongly.
Lipids
Cholesterol is a lipid. The word “lipids” comes from the Greek for fat, “lipos”. Oils and fats can be considered lipids, but fats are usually solid at room temperature, while oils tend to be liquid. We attribute cholesterol to fats because it is usually solid.
Lipids make up a vital part of the human body. They are produced by the body or derived from diet. Lipids are essential for energy production, which is widespread, and are present in every cell. They form a main part of every lipoprotein particle. Lipids must be transported to their sites of use and then destroyed to produce energy. Transporting them to the required location is essential.
VICY structures of main lipid molecules: V-like phospholipid, I-like fatty acid, C-like cholesteryl ester, and Y-like triglyceride.
Fatty Acids
There are several classes of lipids.
The simplest fatty acids are chains of hydrocarbon units between the terminal hydrocarbon and carbonyl groups. Fatty acids, in the form of triglycerides, account for over 90% of the dietary fat. The bonds between the groups can be either single or double, which results in different chemical and physical properties. The more double bonds a fatty acid contains, the more fluid it is. Fatty acids that only contain single bonds between carbon atoms are less fluid, and, at physiological temperatures, can even become solid. They are called saturated fatty acids. Stearic acid, which is mostly derived from animal fats, is the most common saturated fatty acid.
There are three main types of fatty acids: monounsaturated, polyunsaturated, and saturated.
Fatty acids that contain a number of double bonds are fluid and belong to oils. These fatty acids are unsaturated. Unsaturated fats are divided into monounsaturated, which have a single double-bond, and polyunsaturated with two or more. The most common monounsaturated fatty acid is oleic acid which is found in high amounts in olive oil. Polyunsaturated fatty acids are mostly derived from sea animals and vegetables – e.g. linoleic acid from fish oil or sunflower oil.
Triglycerides
Triglycerides, also known as triacylglycerols, are more complex molecules. They are made up of three fatty acids attached to a backbone of glycerol. The molecule of triglyceride is hydrophobic and does not have any hydrophilic components. Triglycerides are a major source of energy that can be either used right away for energy production or stored in the body for meager times.
When the body needs energy, triglycerides derived from the diet or stored in adipocytes (which are fat cells) are broken down into fatty acids and glycerol by enzymes called lipases - proteins that break down lipids. The fatty acids are quickly absorbed by the muscle cells and tissues, where they can be used to generate energy. This is done by producing adenosine triphosphate (ATP), a biological molecule which can be used to power many chemical reactions. The body’s process for producing energy from fatty acids is known as beta-oxidation.
What It Is
Adenosine triphosphate (ATP) is a molecule which gives energy to cells in order to perform different functions such as muscle movements, nerve signals, and the production of other biomolecules, like proteins, DNA and RNA. It can be found in all living things and is known as the “molecular currency” that moves energy within cells. When it is used up, it turns into adenosine diphosphate (ADP) or adenosine monophosphate (AMP).
Nicotinamide adenine dinucleotide phosphate (NADP) is a reduced form of a coenzyme which plays a major role in the production of ATP by all living cells. Coenzyme is a molecule that helps enzymes to catalyze biochemical reaction.
Sugars and triglycerides are the primary sources of energy.
The body stores triglycerides as an energy reserve. Excess calories that are not immediately required for energy production can be converted to triglycerides and then stored in fat (also called adipose) tissues for later use. These stored calories can be used during fasting periods or times when energy requirements are higher, like during exercise. Triglycerides are important in providing energy to the body and as a storage for excess calories.
Interesting Numbers
Every day, an adult human uses approximately 50 kilograms of ATP. The majority (about 45 kilograms) is used for the basal metabolism. Approximately 10,000,000 molecules ATP are produced and consumed by each cell per second.
Sugars are another important source of energy. In the process of glycolysis, sugars are broken down into glucose molecules to produce ATP and NADH. This occurs in the cells’ cytoplasm and is the initial step of respiration. These products are then used in the subsequent steps of cellular metabolism to produce energy-rich ATP.
Sugars are stored in the body at a much lower rate than lipids. Glycogen is a substance that can be made from sugars in excess and stored by animals and humans. Glycogen is a polymer with a high degree of branching made up of glucose molecules. When the body requires energy, the glycogen is broken into glucose which is then released into the bloodstream and used as fuel by the cells. Glycogen helps regulate blood sugar and can be replenished by carbohydrates.
Phospholipids
Phospholipids, another type of lipid molecule, are a major component of the cell membranes which separate cells. Each phospholipid molecule has hydrophilic and hydrophobic parts which are, respectively, called heads and tails. The cell membrane is made up of two layers of phospholipids with the hydrophilic heads facing the outside and the hydrophobic tails facing the inside. This arrangement creates an obstruction that prevents molecules which are water soluble from passing through the cell membrane. The phospholipid cell membrane contains proteins and other molecules that regulate the movement of substances in and out of the cell. This selective permeability enables cells to maintain an internal environment and carry out vital functions, such as nutrient absorption, waste removal, and communication with other cell types.
Besides their role in the cell membrane, phospholipids are also important in subcellular structures called organelles. Membranes that are similar to the ones that separate cells from their surroundings are used to separate these structures from the rest of a cell. When triglycerides or other hydrophobic fats are stored within a cell, they are surrounded by a monolayer of phospholipids. By providing a barrier to the outside environment, phospholipids play an important role in maintaining cell integrity and function.
Is cholesterol innocent?
Sterols
Sterols are another important class of lipids. Cholesterol is undoubtedly the most known sterol. Sterols play an important role in the structure of cells and are another essential component of cell membranes. Sterols are also required for various physiological processes, such as the synthesis of hormones, vitamin D, and bile acids. Sterols are also found in plants, the most common of which are sitosterol, campesterol, and stigmasterol. These are nutrients that can be absorbed from food, and they are found in the human body at much lower levels than cholesterol.
Sterols are available in two forms: free (unmodified) and esterified. Cholesteryl ester is the most common among esterified sterols. It is composed of cholesterol and a fatty acid. Cholesteryl esters are present in many types of tissues, such as the liver, the adrenal glands, and the intestines. These molecules play an important part in the processing of cholesterol by the body. Cholesteryl esters are often formed when cholesterol is absorbed by the body from food or is produced in the liver. They can be used for storage and transportation. These molecules, like triglycerides, can be stored within cells until needed for other metabolic processes.
What It Is
Ester is an organic substance that is made by replacing the hydrogen atoms (H) in at least one hydroxyl group (OH) with another chemical group.
Cholesteryl ester has a fatty acid part that takes the place of the hydroxyl group in cholesterol.
Glycolipids cover the surface of cells and lipoproteins in a forest-like fashion.
Glycolipids are a type of lipid molecule containing a sugar (carbohydrate) ring. They play an important role in cell signaling and recognition. Glycolipids are composed of a hydrophilic carbohydrate head and a hydrophobic lipid tail. The tail anchors the molecule onto the membrane while the head is responsible for interactions with the surrounding environment. The carbohydrate head can be of different sizes and complexity. It may consist of a single sugar or a complex chain. Glycolipids play a key role in cell communication. They are markers that appear on the cell surface, which allow cells to interact and recognize one another. Glycolipids play an important role in the signaling pathways of cells. They help to transmit signals between the cell’s outside and its inside.
Sphingolipids and glycolipids are two other lipid classes that play an important role in humans. Sphingolipids are important for signaling and communication in cells. They are found in the cell membranes. Sphingolipids are made up of a sphingosine, which is an amino alcohol with a long chain, and a fatty acid chain attached to the amino group. Sphingolipids are involved in many cell processes including cell growth and differentiation, apoptosis, and inflammation. Sphingolipids are also important in the immune system, by regulating both the activation of immune cells and their function.
Sphingomyelin is one of the best-known sphingolipids. It is present in high concentrations within the myelin that surrounds the nerve cells. Sphingomyelin is a sphingolipid that helps insulate nerves and transmit electrical signals along the axons. Ceramide is another important sphingolipid, produced from the breakdown of sphingomyelin. Ceramide is known to regulate cell death, survival, and inflammation.
Energy treasure chest: triglycerides, represented in green, are a vital source of energy. They are stored beneath a layer of phospholipids (in grey), with small amounts of cholesterol (in yellow) present within this layer. Within the core of the triglycerides, cholesteryl esters (in pink) can be found.
Interesting Numbers
The average energy content in fats is 9 kcal/g. The average daily intake of fats should not exceed 30% of the total daily calories. This is 70 grams of fat per day based on 2,000 kcal of energy consumed per day.
Although lipids are important energy sources, they differ in terms of their energy-producing capacity. The caloric contents of different lipid classes are quite variable. Triglycerides are the most common type of dietary fat and contain 8–9 kcal/g. The fatty acids that are the building blocks of triglycerides also contain 8–9 kcal/g. The caloric value of fatty acids is affected by their length and saturation. Saturated fatty acid tends to be more calorically dense than unsaturated. In addition, the energy content of fatty acids increases as the chain length increases. Phospholipids have a lower energy density and contain only 4–5 kcal/g. Sterols such as cholesterol do not have any calories because they are not used for energy.
History
Identification of cholesterol
Francois Poulletier de la Salle, a French chemist, first identified cholesterol in a solid form in 1769. The chemist named the substance “cholesterol,” after the Greek words “stereos” meaning “solid” and “khole” meaning “bile” as its solid form was found in the animal bile. His work was never published and the attribution is only known through his collaborators.
After studying patients suffering from gallbladder stone disease, Michel Eugene Chevreul finally named the compound “cholesterine” in 1815. It was renamed to cholesterol in 1929 due to its chemical composition.
Chevreul was not just any scientist. He believed that man was capable of infinite perfection, both in morals and in physical matters, and that science had unlimited power. He saw the Eiffel Tower as a living synthesis, combining all of the acquired knowledge and experience accumulated over centuries. In his last years, he loved to visit the Champ de Mars and watch the construction of the Universal Exposition of 1889.
He explored all the unknown areas of organic chemistry and biochemistry through his remarkable research into animal fats. He invented stearic candle between 1828 and 1831. This discovery revolutionized domestic lighting and enriched thousands of people without him ever thinking about the profit. His institute only awarded him a 12,000-franc prize.
Chevreul was elected a member of the French Academy of Sciences in 1826. He attended every session and missed none for the next 63 years. Chevreul attributed his remarkable longevity to his love of work, his sobriety, and his culinary principles. On August 31, 1886, the centenary of the “Nestor” of chemistry, who lived under three republics and four kings, was honored with a large ceremony.
Friedrich Reinitzer, a German chemist, published the molecular formula for cholesterine in 1888. It was C27H46O. Chevreul, who was alive at the publication of Reinitzer, died at the Jardin des plantes in Paris on Tuesday, 9 April 1889 at 1 o’clock morning after living for 102 years, 7 months, and 8 days. He was the oldest scholar in the world.
It was not until the 20th century that cholesterol was recognized as a component of human blood and tissues, and its role in health and disease was studied.
Interesting Numbers
Michel-Eugene Chevreul, one of the pioneers of cholesterol research, is among the 72 scholars who have their names inscribed on the Eiffel Tower’s first floor in Paris. On the north-facing side, he is number 14.
Proteins
A deeper understanding of cholesterol requires an appreciation for proteins, another type of biomolecule. Proteins consist of long chains of amino acids linked together and serve various roles within organisms – doing chemical reactions, copying DNA molecules, responding to environmental changes, providing structure and organization in cells and organisms, moving molecules throughout the body as well as transporting essential elements like vitamins. Their sequence is determined by genetic code. Furthermore, polypeptides – long chains of amino acids linked together – make up proteins while some have additional parts attached such as sugars and are, in this case, termed glycoproteins.
Proteins perform various functions. Once produced, however, proteins only last briefly before degrading and recycling by cells. They play an integral part in cell processes with animals needing protein consumption to obtain essential amino acids their bodies cannot produce themselves.
2Enigmatic World of Cells and Organs
Cells
Lipids are involved in the functioning of every cell. Similarly, certain cells are crucial for the regulation of lipids and lipoproteins. In the context of heart disease, certain cell types are especially important, but we don’t fully understand how they work. These include, first of all, hepatocytes, enterocytes, endothelial cells and macrophages.
Hepatocytes
Hepatocytes (also called hepatic cells) are the cells that make up about 80% of the mass of the liver. The name comes from the Greek “hepar,” meaning “liver,” and “kutos,” means “hollow vessel.” These cells have many important functions. They make and store proteins, metabolize carbohydrates into other molecules, and produce cholesterol, bile acids, and other lipids. These cells also make bile and help eliminate harmful substances from the body.
The main cell types involved in cholesterol processing are hepatocytes, enterocytes, endothelial cells, and macrophages.
Hepatocytes are cubical cells with sides that are 20–30 μm wide. Comparatively, they have more smooth endoplasmic membranes (which are involved in producing biomolecules) than other cells. The endoplasmic membrane helps hepatocytes to attach proteins to carbohydrates and lipids. Hepatocytes also produce many serum proteins and lipoproteins. The liver secretes hormones known as hepatokines, converts carbohydrates into fatty acids, and makes triglycerides out of fatty acids and glycerol. The liver also makes cholesterol from acetate and produces bile acids. Bile acids can only be synthesized by the liver.
Enterocytes
The most abundant intestinal cells are enterocytes. The name derives from the Greek “enteron,” meaning “intestine,” and “kutos,” meaning “hollow vessel.” They are oblong, about 40–50 μm high with an average volume of 1,400 μm3. The enterocytes are responsible for absorbing nutrients and other substances from food. The surface of enterocytes is coated with digestive enzymes, and they have tiny hairs that protrude into the interior of the small intestine and increase the surface area. These structures are called intestinal villi. Enterocytes can then take up small molecules from the intestines such as proteins, sugars, and lipids. These cells release hormones as well and play several roles. They absorb lipids, take in ions such as sodium and calcium, and absorb water and sugar. They also break down proteins into amino acid chains, reabsorb bile salts, and release immunoglobulins to the intestines. An enzyme called pancreatic lipase breaks down lipids in the intestine, which then move into enterocytes. The smaller lipid molecules are absorbed into the blood vessels of the intestine, while the larger ones are converted into lipoproteins known as chylomicrons. They are then released into the lacteals, which are lymphatic capillaries located in the villi.
What It Is
Lacteals are lymphatic capillaries in the villi of the small intestine.
Intestinal villi are tiny finger-like parts that stick out into the inside of the small intestine.
Endothelial Cells
The endothelial cells found in blood vessels control fluids and substances entering and leaving tissues. The word “endothelium” derives from the Greek words “endon,” meaning “inside,” and “thele,” meaning “teat” or “nipple.” These cells, however, are more than just a barrier. They also aid in processes such as blood vessel formation, inflammation, and blood coagulation. Endothelial cells play an important role in maintaining healthy blood vessels and heart. These cells are present in all blood vessels, and they rely on the soluble gas nitric oxide to function.
The endothelium is a single layer of endothelial cells lining the inner surface of blood vessels. It serves as a protective barrier, keeping the blood from coming into direct contact with the rest of the vessel walls. The endothelium has many other functions, including preventing blood clots, regulating blood pressure, and assisting with healing and inflammation.
Interesting Numbers
The endothelium, although invisible, is a very large part of our body. It is made up of trillions and trillions of cells. On an average, it covers nearly 3 m2.
Macrophages
Macrophages, which are large white cells in the blood, help to fight infections and injuries. The name comes from the Greek words “makros,” meaning “large,” and “phagein,” meaning “eat.” It can be translated as “big eaters.” The macrophages work by engulfing and then digesting harmful agents such as cancer cells and bacteria. Macrophages can be found in every tissue and are involved in the body’s specific immune response as well as its general defense system. They can reduce inflammation and promote tissue repair. Different macrophages have different functions. These cells have a diameter of about 20 μm and can be distinguished by the proteins they express at their surface.
Platelets
Platelets (or thrombocytes) are white blood cells which help stop bleeding after a blood vessel has been injured. Platelets are white blood cells without a nucleus. They come from bone marrow and lungs, and they travel through the blood. Platelets form a plug when there is an injury or cut to a vessel. Platelets also help prevent blood clots in healthy blood vessels.
Adipocytes
Adipocytes are also known as fat cells. They store energy in lipids. The word comes from the Latin “adeps,” which means “fat,” or “lard.” There are two types of adipocytes: brown and white cells. The white cells are from 20 μm to 0.3 mm wide and contain large droplets of lipid, while the brown cells are smaller. The droplets are primarily composed of triglycerides and also of cholesteryl esters.
Organs
Cells create organs that are involved in the production, transport, and removal of lipids and lipoproteins. The most prominent of these organs are blood arteries. Additionally, three other organs – the liver, heart, and intestine – also play central roles in the regulation of these processes.
Arteries
The arteries are an important part of cardiovascular systems, as they distribute oxygen-rich blood to all parts of the body. The tube-like blood vessels and muscles within them ensure that organs, tissues, and cells receive the oxygen and nutrients needed to function properly. The heart pumps oxygenated blood into the largest arterial system in the body – the aorta. This vessel then branches into smaller arteries to reach every part of the body. The coronary arteries supply blood to the heart. Other arteries deliver blood to specific organs and areas in the body. The central nervous system sends signals to the arteries that cause them to dilate or constrict, affecting blood pressure. By adjusting the muscle walls, they help regulate blood pressure. Arteries differ from veins which carry deoxygenated blood back to the heart. Veins only have a thin layer of muscle tissue inside and use valves to keep blood flowing.
The arteries have three layers: the inner layer, called tunica intima (“inner coat” in Latin), contains tissue with elastic fibers, the middle layer, called tunica media (“medium coat” in Latin) is mainly smooth muscle, which allows the arteries to be tightened or opened, and finally, there is an outer layer, called tunica adventitia (“additional coat” in Latin), that interacts with other tissues including nerves. The inner layer is composed of one layer of endothelial cells and is supported internally by an elastic lamina. Endothelial cells are directly in contact with blood flow. The inner coat is a transparent, colorless, thin layer that can stretch. It is composed of a layer of flat, oval, or spindle-shaped cells, called pavement endothelium. It also contains a delicate layer of connective tissue, with branched, flat cells between them, and an elastic layer.
Arteries can be arranged in arterial trees and classified according to their size, function, and location. Elastic arteries are the largest arteries of the body. The aorta is one of these arteries, as it is the main blood vessel that carries the blood from the heart to other parts of the body. Elastic arteries are characterized by a high concentration of elastin, a protein that allows them to contract and expand with every heartbeat. This allows for a constant flow of blood to be maintained throughout the body.
The arterial wall is composed of three layers: the intima, media, and adventitia. The intima is the layer just beneath the endothelial cells, followed by the media and adventitia.
Muscular arteries are smaller than elastic arteries but larger than arterioles. Their walls have more smooth muscles, which allows them to contract or dilate in response to changes in blood pressure. Muscular arteries deliver blood to specific organs or tissues. Arterioles are small branches from muscular arteries leading to capillaries. They are characterized by a thin layer of smooth muscle in their walls, which regulates blood flow to capillary beds. Capillaries are tiny vessels that connect arterioles and venules. They have thin walls which allow the exchange of oxygen and nutrients between tissues and blood.
Heart
The heart is a muscular organ that pumps blood throughout the body. The heart brings oxygen and nutrients to the tissues and removes waste products like carbon dioxide. The heart in humans is the size of a closed fist. The heart beats because of an electric current generated by pacemaker cells.
The heart is a double pump. It has four chambers which work together to pump the blood around the body. The right side of the heart pumps oxygen-poor blood to the lungs where it is oxygenated. This oxygen-rich blood is then pumped back to the body by the left side of the heart via a network of arterial vessels. These arteries are divided into capillaries that supply oxygen and nutrients directly to the cells. The heart collects the deoxygenated vein blood and sends it to the lungs.
Interesting Numbers
Heart pumps five liters of blood per minute. The diameter of the coronary arteries is between 2 and 5 mm. They pump from 0.25 to 1.0 liters of blood per minute.
The heart can be visualized as a double H-pump, where two pumps operate in perfect coordination.
The heart regulates metabolism by responding to the changes in energy demand. At rest, the heart normally beats 72 times per minute. However, exercise can increase that rate in order to provide more oxygen and nutrients for working muscles. During sleep or at rest, the heart rate decreases to conserve energy. The heart is also crucial in maintaining fluid balance. It regulates blood pressure by changing its pumping rate and strength in response to changes within blood vessels.
Liver
The liver is the heaviest of all the organs in the body and also the largest gland. Hepatocytes make up the majority of the liver’s volume (70–85%). The liver plays a principal role in how the body uses lipids. The liver helps take up, produce, and secrete various types of lipids within the body. This is done by four processes: burning fat as energy, producing different types of lipoproteins, making cholesterol and phospholipids, and converting carbohydrates into triglycerides to store.
The liver makes and secretes different types of lipoproteins. It also removes lipoproteins from the blood using special protein receptors. Bile, a yellow–green liquid that serves to break down fats, is produced by the liver to aid digestion. Some of the bile is sent straight to the small intestinal tract, while some remains in the gallbladder.
What It Is
Bile, also called gall, is a yellowish-green liquid constantly produced by the liver to help break down fats in the intestine. The gallbladder stores and concentrates it and then releases it into the small intestine.
Gallbladder is a small organ which holds bile and then releases it into the small intestine for fat digestion. It is pear-shaped and it sits below the liver. The gallbladder receives the bile from the liver and then sends it into the small intestine. Gallstones may form in the gallbladder, causing pain.
Intestine
The small intestine, which is part of the digestive tract, helps absorb nutrients from food. The small intestine is 6 m long and located between the stomach and the large intestine. It has three sections – the duodenum, jejunum, and ileum. The duodenum prepares nutrients for absorption, the jejunum absorbs nutrients, and the ileum takes up bile salts and leftover digestion products. Pancreatic lipase breaks down fats in the intestine into fatty acids and glycerol. Bile is produced by the liver, and it helps the lipase to do its work. It attaches to fats to make them easier to break down. The lipase, however, is hydrophilic while the fats, on the other hand, are not. Bile therefore helps to mix the two together so that the fats may be broken down and absorbed.
Villi at the surface of the intestine help absorb lipids. Each villus measures between 0.5 and 1.6 mm in length, with many smaller projections known as microvilli. The microvilli are what create the striated or brush border on the surface. This increases the amount of surface that can absorb nutrients.
An artistic view of the surface of a hepatocyte, an endothelial cell, an enterocyte, and a macrophage covered with proteoglycans (clockwise from the top left).
3Shadowy World of Diseases
Atherosclerosis
The reason why we are interested in hepatocytes, enterocytes, macrophages, and other cells and organs dealing with cholesterol, lipids, and lipoproteins is that their malfunction can cause atherosclerosis. This word is derived from the Greek “athero” meaning “paste” or “gruel”, and “sclerosis,” which means “hardness.” The Greek suffix “osis,” which describes a diseased state, is used here, too. Atherosclerosis, then, is a disease that involves the hardening of arterial walls due to the accumulation of cholesterol. Parallel to this, other substances deposit in the arterial walls. Over a long time, atherosclerosis can lead to heart attack and stroke.
Atherosclerotic Lesions
Lesions and plaques are the terms used to describe sites affected by atherosclerosis. These lesions are found in the inner linings of arteries that have been damaged. Atherosclerotic lesion slowly develops over many years to become life-threatening. Different factors can accelerate this pathological progression, including genetic deficiencies or an unhealthy lifestyle.
Atherosclerosis involves a buildup of lesions inside the arteries. This causes the latter to narrow and become harder. The lesion is composed of cholesterol and other lipids and substances which accumulate over time on the inner wall of the arteries. The lesions develop in the arterial intima and are covered by a cup made of proteins. The more lipid is present in the lesion, the more likely it is to rupture. The rupture can block blood flow to organs like the heart, brain, and kidneys as it continues to accumulate. This can cause serious health issues such as heart attack, stroke, and kidney failure.
Atherosclerotic lesions are microscopic injuries of the arterial walls caused by lipids. The lipids act like foreign bodies and cause irritation to the arterial tissue, resulting in a type of chronic inflammation. We have all experienced acute inflammation. It can cause achy backs, abscesses in the mouth, or skin rashes. It is visible, uncomfortable, and often painful. Redness is due to an influx of blood into the area. Swelling is the result of immune cells that are working to heal and prevent infection or injury. These symptoms are part of the natural healing process, and they stop once the process is complete. Chronic inflammation, on the other hand, does not cease for a very long time. It continues when healing is impossible. Atherosclerotic lesions are injuries to the arterial walls where chronic inflammation occurs.
Atherosclerotic lesions develop over a lifetime, starting early. Prenatal atherosclerosis may also affect the development and growth of the arteries within the fetus before birth. This condition may have serious consequences for the developing fetus. Prenatal atherosclerosis may cause a variety of complications including fetal development restriction, preterm delivery, and stillbirth. Prenatal atherosclerosis is diagnosed using ultrasound imaging, which measures blood flow in the fetal arteries. The discovery of prenatal atherosclerosis followed that of atherosclerotic lesions in young adults made in the 1950s in young victims of the Korean War.
