Dyslipoproteinemias in atherosclerosis, thrombosis and restenosis after coronary angioplasty.

Lipids play a vital role in normal metabolic function in mammals. However, dyslipoproteinemias have been implicated in the pathophysiologic process of atherogenesis, thrombogenesis and restenosis after interventional procedures. Lipoproteins provide important chemical linkages among these three complex phenomena. Lipoproteins participate in atherogenesis and play a major role in plaque fissuring, the pathophysiologic common denominator of acute ischemic syndromes. Thrombogenesis is majoraly affected by the action of lipids on platelets, coagulation and fibrinolysis. LDL tend to destabilize platelet membrane activity, macrophages, endothelial and smooth muscle cell function; HDL tend to reverse these abnormalities. The metabolism of arachidonic acid, a metabolite of the essential polyunsaturated lipoprotein, linoleic acid, is integral to platelet and endothelial cell membrane formation, via the cyclooxygenase-prostanoid pathway. Arachidonic acid also is metabolized by the lipoxygenase-leukotreine pathway in neutrophils and monocytes. The relationship of dyslipoproteinemias (increased LDL and Lp(a); decreased HDL) to restenosis after angioplasty has been reported, though there is not universal agreement about causality. Lipid lowering regimens and other pharmacotherapy have had favorable effect slowing the rate of atherogenesis, decreasing the frequency of cardiac events (perhaps by "stabilizing" vulnerable plaques) and causing regression in some atheromata. The salutary effect of lipid-lowering agents upon the incidence of restenosis after angioplasty is problematic. Some investigators have found a statistically significant correlation, while others have not; but studies have not been standardized. In conclusion, the study of lipid metabolism across a wide range of physiochemical activities and the interaction of these phenomena describe complex, genetically determined linkages which instruct (and often humble) investigators in their study of lipids in health and disease.