Role of platelets in atherogenesis: relevance to coronary arterial restenosis after angioplasty.

There is now considerable evidence to suggest that some aspects of early lesion formation and later lesion growth are a reaction to injury. Hemodynamic factors are important in determining the site of injury and may produce injury directly. Injury can lead to atherogenesis in animal models as well as in humans. Superficial injury exposes the subendothelium, allowing platelet adhesion, which at high shear rates is dependent on vWF. Platelet adhesion and degranulation release PDGF, which stimulates smooth muscle cell proliferation, synthetic functions, and vasoconstriction. LDL stimulates smooth muscle cell growth as well as damages endothelium in some experimental systems. Thus, a link is provided between platelet and lipid involvement in atherosclerosis. Direct evidence for a role of platelets in atherogenesis comes from studies in which animals were treated to reduce platelet number or function or in which platelet function is genetically impaired (pigs with von Willebrand's disease). In these models, reduced platelet function is associated with less atherosclerosis. Deeper injury exposes collagen, with subsequent platelet aggregation, thrombin and fibrin generation. The role of reduced production of PGI2 and fibrinolytic agents following severe damage is unknown. Deep injury to the vessel occurs during plaque fissuring, the pathologic process underlying most cases of myocardial infarction, unstable angina, and some cases of sudden death. Angioplasty produces amelioration of many patients' symptoms and is safe. However, acute occlusion occurs occasionally, and restenosis in the first year occurs in some 30 percent of patients treated. Angioplasty damages the arterial wall, with endothelial denudation and intimal and medial splitting. Why does this, and plaque injury, by stimulating platelet deposition, not produce more restenosis? Changes in arterial anatomy are likely to be important: the increase in vessel diameter and in blood flow produce conditions less favorable for thrombotic or arteriosclerotic restenosis.