高脂血症と線溶系

Abstract

The effect of free fatty acids (FFAs) on fibrinolysis and platelet aggregation was studied and pathological roles of FFAs were discussed in relation to FFA regulating enzymes in blood vessel wall. Fibrinolysis was estimated in vitro using suspension of fine particles of human fibrin as a substrate. Unsaturated FFAs suppressed fibrinolytic action of plasmin. The most potent inhibitor among tested was oleic acid (66% inhibition at 5mM). Saturated FFAs were far less effective. The inhibitory effect of oleic acid was not seen when fibrin was replaced by casein or TAMe. Binding of oleic acid to fibrin showed a direct relation to its antifibrinolytic activity. Also, formation of plasmin-fibrin complex in the reaction mixture was augmented by oleic acid. Thus the FFA effect seems to be exerted through modification of E-S complesx formation. Some FFAs, particularly saturated ones, are known to aggregates human platelets. Stearic acid enhanced the epinephrine-induced aggregation at low concentrations in which it by itself has no effect on platelets. Although these effects of FFAs may be diminished in the presence of albumin, a thrombotic nature of FFAs in a certain circumstance is suggested. Lipase and triglyceride synthetase in the low-speed supernatant fraction of rat aorta were greatly modified by Ca++; i. e. the former was enhanced and the latter inhibited. These findings implies the importance of relationship between platelet functions (adhesion, aggregation and release reaction) and FFA mobilization at the surface of atheromatous lesion.