Current understanding of pathogenesis of coronary artery disease and its future implications.

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.