Modulation of Rabbit Platelet Aggregation and Calcium Mobilization by Platelet Cholesterol Content

Hypercholesterolemia is one of the major contributing factors in atherosclerosis and the development of cardiovascular disease Platelets from hypercholesterolemic rabbit have an increased cholesterol content and a hypersensitivity to endogenous aggregating agonists Although rabbit has been widely used in studies of hypercholesterolemia. the precise role of platelet cholesterol in rabbit platelet activation has not been studied In the present study, to determine the direct role of cholesterol on rabbit platelet activation. we examined the effect of in vino modulation of cholesterol content on platelet activation Cholesterol-depleted rabbit platelets by the treatment methyl-beta-cyclodextrin showed decreased platelet aggregation by physiological agonists such as thrombin, adenosine diphosphate. and collagen The in of thrombin-induced aggregation in cholesterol-depleted platelets was restored by cholesterol tepletion in platelets The cholesterol depletion also inhibited Ca2+ mobilization, which plays a pivotal role in the platelet activation induced by physiological agonists We showed that the Ca2+ influx pathway is strongly suppressed by cholesterol depletion more than Ca2+ release from intracellular Ca2+ stores in platelets stimulated with thrombin Furthermore, platelet aggregation induced by PMA. a potent protein kinase C activator. was also depressed by cholesterol depletion On the other hand cholesterol enrichment in platelets augmented thrombin-induced aggregation and Ca2+ mobilization These findings suggest that cholesterol plays a critical role in regulating rabbit platelet activation and provides fundamental information regarding hypercholesterolemia-mediated effects on cells in the rabbit model