Atherosclerosis and Acute Coronary Syndromes
Toronto General Hospital Research Center
Toronto, ON, Canada
|• ||Coronary Artery Disease is the leading cause of mortality in the western world .|
Acute Coronary Syndromes
|non-ST elevation myocardial infarction (non-STEMI)|
|ST elevation myocardial infarction (STEMI)|
|Same pathophysiology for the three clinical conditions|
|Different clinical features, therapies, and prognosis for each|
|• || Atherosclerosis has been shown to be present as far back as in ancient Egypt.|
|• ||Jean Lobstein used the term arteriosclerosis in a 1829 pathology monograph.|
|• || Carl Rokitansky promoted a thrombogenic theory of atherosclerosis in 1852.|
|• || Rudolf Virchow in 1858 identified intimal deposits. He focused on cells, connective tissue, and ultimately vascular degeneration .|
|• || In the first decade of the 20th century, Alexander Ignatovski and Nikolai Anitschkov showed that egg yolk and pure cholesterol caused atherosclerosis in experimental animals.|
The lesions of atherosclerosis were identified well before establishing an association between the
histopathology observations found at autopsy and the clinical syndromes of coronary artery disease,
cerebral vascular disease, and peripheral vascular disease.
Angiograms show irregular borders and intraluminal lucency in cases with rupture, hemorrhage and
Elegant, detailed morphological studies by pathologists provided the basic knowledge to direct
biochemical, cellular and molecular investigations into the pathogenesis of atherosclerosis and acute
Today, there is intense study of each of the morphological components of the plaque to understand cell
function, lipid deposition, inflammation, immune activity, neovascularization, matrix remodeling and
fibrous cap rupture .
Vascular cell and molecular biology studies involving state-of-the-art technologies are providing
information on the pathogenesis, diagnosis and treatment of acute coronary syndromes. These technologies
include imaging (static and live cell imaging to understand molecular events), genomics, proteomics, and
interdisciplinary approaches involving engineering, computational biology, biomaterials, and clinical
Endothelial dysfunction promotes loss of thromboresistance and formation of mural thrombi.
Endothelial dysfunction leads to erosion and fissure formation on the surface of complicated
fibroinflammatory lipid plaques . These promote plaque rupture .
Endothelial repair regulated, in part, by hemodynamic shear stress
may help to stabilize the
surface of an unstable vulnerable plaque
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- Davies MJ, Thomas A. Thrombosis and acute coronary artery lesions in sudden cardiac ischemic death. N Engl J Med 1984; 310:1137-1140.
- Davies MJ, Woolf N, Rowles PM, Pepper J. Morphology of the endothelium over atherosclerotic plaques in human coronary arteries. Br Heart J. 1988;60:459-64.
- Kolodgie FD, Virmani R, Burke AP et al. Pathologic assessment of the vulnerable human coronary plaque. Heart 2004; 90:1385-1391.
- Dickson BC, Gotlieb AI. Endothelial dysfunction and repair in the pathogenesis of stable and unstable fibroinflammatory atheromas. Can J Cardiology 2004; 20, Suppl B:16B-23B.
- Aikawa M, Libby P. The vulnerable atherosclerotic plaque. Pathogenesis and therapeutic approach. Cardiovascular Pathology 2004;13125-138.
- Vyalov S, Langille BL, Gotlieb AI. Decreased blood flow rate disrupts endothelial repair in vivo. American Journal Pathol 1996;149:2107-18.
- Walpola PL, Gotlieb AI, Cybulsky MI, Langille BL. Expression of ICAM-1 and VCAM-1 and monocyte adherence in arteries exposed to altered shear-stress. Arteriosclerosis Thrombosis and Vascular Biology 1995;15:2-10.
- Cunningham K, Gotlieb AI. The role of shear stress in atherogenesis. Lab Invest 2005; 85:9-23.
- Lee JSY, Gotlieb AI. Microtubule-actin interactions may regulate endothelial integrity and repair. Cardiovascular Pathology 2002;11:135-40.
- Lee JSY, Gotlieb AI. Understanding the role of the cytoskeleton in the complex regulation of the endothelial repair. Histol Histopathol 2003:18;879-887.
- Lee TY, Gotlieb AI. Early stages of endothelial wound repair: conversion of quiescent to migrating endothelial cells involves tyrosine phosphorylation and actin microfilament reorganization. Cell Tissue Res. 1999;297:435-50.
- Lee TYJ, Gotlieb AI. Microfilaments and microtubules maintain endothelial integrity. Microscopy Research and Technique 2003;60:115-25.