Platelet prostacyclin receptors in myocardial infarction

Research Project

Project/Area Number	04671441
Research Category	Grant-in-Aid for General Scientific Research (C)
Allocation Type	Single-year Grants
Research Field	Laboratory medicine
Research Institution	School of Medicine, Tokai University
Principal Investigator	ANDO Yasuhiko Dpt.Clin.Path.Tokai Univ.Prof., 医学部・臨床病理, 教授 (50051470)
Co-Investigator(Kenkyū-buntansha)	MIYACHI Hayato Dpt.Clin.Path.Tokai Univ.Assist.Prof., 医学部・臨床病理, 講師 (20174196)
Project Period (FY)	1992 – 1993
Project Status	Completed (Fiscal Year 1993)
Budget Amount *help	¥1,800,000 (Direct Cost: ¥1,800,000) Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000) Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywords	Prostacyclin receptor / Hyperlipidemia / Prostacyclin sensitivity / cAMP / Platelet / Iloprost / Iloprost / 血小板凝集能抑制作用 / Binding Assay / 血栓症
Research Abstract	In the development of arterial thrombosis such as myocardial infarction or cerebral thrombosis, blood platelets are believed to play a major role. Prostacyclin (PGI_2) is synthesized by the action of prostacyclin synthetase in endothelial cells and inhibits platelet functions via its ability to elevate platelet cyclic AMP(cAMP) and block calcium mobilization. It is therfore worthwhile to study interaction between platelets and PGI_2 by using Iloprost, a stable PGI 1 analogue, in patients with hyperlipidemia in that arterial thromboses are frequently encountered. Twentyeight patients with hyperllipidemia including 14 patients with type II a, 10 with type II b and 4 with type IV were involved in this study. Concentrations of PGI_2 which can cause 50% inhibition of collagen-induced platelet aggregation (10mug/ml collagen) were significantly lower in platelets from patients with type II a and type II b than control. Number of binding sites of [H^3N-Iloprost on platelet membranes was found to be higher in patients with type II a and type II b than control group. On the contraly, platelet cAMP concentrations, measured by ELISA, elevated less in platelets from hyperlipidemic patients after incubation with PGI_2 and IBMX, a potent phosphodieste-rase inhibitor. From these results it is suggested that there might be some abnormalities in signal transduction in platelets from hyperlipidemic patients. However, further studies are necessary to elucidate the detailed mechanism of PGI_2 action on those platelets.