Coronary Artery Disease

From Biology to Clinical Practice

Dimitris Tousoulis

• Publisher: Academic Press
• Year: 2017
• ISBN:
  9780128119372
• Topic: Medicina
• Subtopic: Cardiología

Coronary Artery Disease: From Biology to Clinical Practice links the most important basic concepts of atherosclerosis pathophysiology to treatment management of coronary artery disease. Comprehensive coverage starts with the basic pathophysiologic mechanisms of the disease, including molecular and genetic mechanisms, cells interaction and inflammation. In addition, sections on novel anti-atherosclerotic therapies and a thorough understanding of the recent trends in clinical management round out this comprehensive tome that is ideal for practitioners and researchers.

By summarizing this novel knowledge and changes in diagnostic algorithm and treatment options, this is the perfect reference for cardiology researchers who want a volume with the most up-to-date experimental trends in the field of atherosclerosis, for cardiologists and physicians who manage patients with atherosclerotic risk factors and established coronary artery disease, and medical students who want to learn the basic concepts of atherosclerosis.

• Delivers a comprehensive connection between basic pathophysiologic mechanisms and the clinical context of coronary artery disease
• Provides a focus on the most important novel evidence in the management of atherosclerosis and coronary artery disease
• Includes sum-up tables at the end of each chapter and clinical scenarios that focus on diagnosis and treatment
• Conveys an understanding of upcoming, novel, experimental and clinical treatments

Chapter 1

Pathophysiology of Atherosclerosis

Outline

Chapter 1.1. Biology of the Vessel Wall

Chapter 1.2. Endothelial Function

Chapter 1.3. Atherosclerotic Plaque

Chapter 1.4. Risk Factors of Atherosclerosis: Pathophysiological Mechanisms

Chapter 1.5. The Role of Inflammation

Chapter 1.6. The Role of Oxidative Stress

Chapter 1.7. Genetics of Atherosclerosis

Chapter 1.1

Biology of the Vessel Wall

Evangelos Oikonomou, Sotirios Tsalamandris, Konstantinos Mourouzis, and Dimitris Tousoulis 1^st Cardiology Clinic, ‘Hippokration’ General Hospital, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece

Abstract

Atherosclerosis is a pathologic process that develops in the arterial wall. Therefore the biology and imaging of the vessel wall is the cornerstone of research, diagnosis, and treatment in patients with atherosclerosis and coronary artery disease. Three functional layers (intima, media, and adventitia) have been recognized that actively orchestrate blood perfusion in tissue and organs; however, changes in the intima layer and especially endothelial damage predispose to atherosclerosis, thrombus formation, and acute coronary events. Over the years additional characteristics have been recognized (i.e., thin cap fibroatheroma, thermal heterogeneity, infiltration with macrophage and inflammatory cells) predisposing to plaque rapture and erosion and acute coronary syndromes, which should orient future research and treatment strategies.

Keywords

Atherosclerosis; Coronary artery disease; Endothelial cell; Intima; Media layer; Thrombus

Contents

Arterial Anatomy

Intima Layer

Endothelium

Basement Membrane

Elastic Membrane

Media Layer

Adventitia

Coronary Perivascular Adipose Tissue

Perfusion of Arterial Wall and the Role of Vasa Vasorum

Biology of Coronary Atheromatous Plaques

Plaque Morphology and Vulnerable Plaque Characteristics

Coronary Blood Flow and Circulation

The Role of Wall Shear Stress

Collaterals and Microcirculation

Conclusions

References

Further Reading

In a simplistic view, the role of arteries is to transfer blood from one site to another merely functioning as tubes. However, this concept has long been overcome and since the mid-19th century it has been recognized that the arterial wall serves multiple functions and can actively regulate blood flow and pressure, tissue perfusion or ischemia, and coagulation, while also participating in atherogenesis formation and progression. Therefore the biology of vessel wall and arterial anatomy has gained research interest.

Arterial Anatomy

Three layers can be identified in the arterial wall from inside to outside: the intima, media, and adventitia, and atherosclerosis process involves primarily pathologic changes in the intima with reactive changes in the media and adventitia.

Intima Layer

The intima layer is made up of the endothelial surface, the basement membrane, and the internal elastic lamina. In the absence of atherosclerosis intima is extremely thin and serves several unique roles orchestrating the functional characteristics and properties of the arterial wall.

Endothelium

Normal endothelium is a thin monolayer of endothelial cells. Its surface in the human body is estimated to be 350 m² with a mass of only 110 g. Many vasoactive substances (i.e., nitric oxide, endothelin 1) are produced by endothelial cells with vasodilating and antithrombogenic actions regulating vascular homeostasis. Importantly, endothelial cells have the unique ability to keep blood liquid and to inhibit activation of the coagulation cascade by the expression of the anticoagulants thrombomodulin, heparin sulfate, and prostacyclin on their surface. On the contrary, in the presence of endothelial damage and dysfunction the balance shifts toward a prethrombotic state and proatherosclerotic changes ensue (Fig. 1.1.1). Interestingly, bone marrow-derived endothelial progenitor cells circulating in the blood stream contribute to neovascularization and re-endothelialization of the injured vessel maintaining vascular function and homeostasis.

Therefore the central role of the endothelium in vascular homeostasis and atherosclerosis progression is discussed in detail in a separate section of this book.

Figure 1.1.1 Endothelial-derived procoagulant and anticoagulant factors. HSPG, heparan sulfate proteoglycan; PA_i, plasminogen activator inhibitor; PGI₂, prostacyclin; t-PA, tissue plasminogen activator; u-PA, urokinase-type plasminogen activator.

Basement Membrane

Basement membrane supports the endothelial monolayer and contains collagen, laminin, fibronectin, and other extracellular matrix molecules. Aging process changes the composition of basement membrane with presentation of smooth muscle cells and fibrillar forms of collagen (collagen types I and III). The extracellular contents of the basement membrane are produced by smooth muscle cells. Intimal thickening characterizes most adult human arteries and does not necessarily accompany atherosclerosis.

Elastic Membrane

Elastic membrane serves as a connection of the intima with the media layer.

Media Layer

This layer is composed of a series of concentric layers of smooth muscle cells interchangeable with layers of extracellular matrix rich in elastin especially in the great elastic arteries such as aorta. Of note, this structure changes as we progress from great arteries to small muscular arteries where the layers of muscular and extracellular contents cannot be readily recognized. In great arteries, the described structure of media tunica serves to store kinetic energy powered by left ventricular systole in a dynamic form, which is attributed latter during diastole.

Adventitia

The adventitia mainly consists of collagen fibrils and a sparse cellular population consisting of fibroblasts and mast cells. In this layer nerve endings and vasa vasorum are observed.

Coronary Perivascular Adipose Tissue

Adipose tissue plays a specific, well-known role in cardiovascular system physiology through the systemic effects of active adipokines that are released into blood circulation or through paracrine signaling of the fat secretome that surrounds the vascular wall. Our recent studies have underlined the significance of a bidirectional interaction between the arterial wall and perivascular adipose tissue and between the epicardial adipose tissue and the myocardium.

A layer of epicardial fat surrounds the major epicardial arteries, which is critical for their function and coronary atherosclerosis progression. Human epicardial adipose tissue biopsies have shown that its gene expression profile changes to a proinflammatory phenotype in the presence of coronary atherosclerosis. Recently, we have proved that perivascular adipose tissue has defense mechanisms whose activation is induced by “rescue signals” sent by the arterial wall in the presence of cardiovascular disease; for example, the expression of adiponectin, an antiinflammatory adipokine, is upregulated in the human perivascular adipose tissue during high oxi...