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Current understanding of pathogenesis of coronary artery disease and its future implications
Insights
Coronary artery disease (CAD) involves atherosclerosis, a condition where plaques build up in arteries. Understanding vulnerable plaques and factors like PAI-1 is key to managing this leading cause of death.
Area of Science:
- Cardiovascular Medicine
- Pathology
- Molecular Biology
Background:
- Coronary artery disease (CAD) is a major cause of death globally.
- Atherosclerosis, a key factor in CAD, involves plaque buildup in artery walls.
- While treatments exist, the pathogenesis and progression of CAD require further understanding.
Purpose of the Study:
- To review the pathogenesis of atherosclerosis and CAD.
- To define characteristics of vulnerable plaques.
- To explore the role of genetic and environmental factors, cell adhesion molecules, PAI-1, and angiogenic factors in CAD.
Main Methods:
- Literature review of atherosclerosis and CAD pathogenesis.
- Analysis of plaque characteristics associated with clinical events.
- Discussion of molecular mechanisms including PAI-1 and angiogenic factors.
Main Results:
- Atherosclerosis involves intimal accumulation of plasma proteins in 'lesion prone areas'.
- Vulnerable plaques feature large lipid cores, thin fibrous caps, and high macrophage density.
- Genetic and environmental factors, cell adhesion molecules, PAI-1, and angiogenic factors (like VEGF) play roles in CAD.
Conclusions:
- CAD is a complex disease with both genetic and environmental influences.
- Understanding plaque vulnerability and molecular pathways is crucial for CAD management.
- Therapeutic angiogenesis presents a potential future treatment strategy for CAD.
Abstract:
Coronary artery disease (CAD) is the most important cause of morbidity and mortality in a population. Percutaneous coronary intervention and coronary artery by-pass grafting have greatly changed the treatment of CAD, still many questions remain unanswered. Atherosclerosis is a normal consequence of ageing but some patients may experience it at an earlier age. As regarding pathogenesis of atherosclerosis, it is described often as a focal process which is diffuse in nature primarily involving the vessel intima. Salient features of 'lesion prone areas' in atherosclerosis include increased endothelial permeability to an intimal accumulation of plasma proteins, including albumin, fibronogen and LDL. The clinical expression of atherosclerotic disease activities is determined by pathologic events leading to coronary thrombosis. A vulnerable plaque has the characteristics of: Extracellular lipid pool occupies a large proportion of overall plaque volume, the fibrous cap which separates the lipid core from luminal blood is thinner within, and high macrophage density. Typically these plaques cause < 50% cross-sectional stenosis of the artery. The contribution of CAD is clearly of both genetic and environmental in origin. An increase in shedding of cell adhesion molecules may be a characteristic of atherosclerotic lesion. There is also suggestion that plasminogen activation inhibitor type I (PAI-1) has an important role in atherogenesis. Angiogenic growth factors and their endothelial receptors function as major regulators of blood vessel formation. Thereapeutic angiogenesis can be achieved by exogenously adding VEGF and/or other angiogenic growth factors.