Inhibition of Thromboxane Biosynthesis and Platelet Function by Simvastatin in Type IIa Hypercholesterolemia

Arteriosclerosis, Thrombosis, and Vascular Biology - Tập 15 Số 2 - Trang 247-251 - 1995
A Notarbartoló1, Giovanni Davı̀1, Maurizio Averna1, Carlo M. Barbagallo1, Antonina Ganci1, Carlo Giammarresi1, Francesco P. La Placa1, Carlo Patrono1
1From the Department of Medicine, University of Palermo (A.N., C.M.B., A.G., C.G., F.P.La P.); the Department of Medicine, University of Catania (M.A.); and the Departments of Hematology (G.D.) and Pharmacology (C.P), University of Chieti, Italy.

Tóm tắt

Abstract Thromboxane A 2 (TXA 2 ) biosynthesis is enhanced in the majority of patients with type IIa hypercholesterolemia. Because simvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor) was previously shown to reduce platelet aggregation and TXB 2 production ex vivo, we investigated TXA 2 biosynthesis and platelet function in 24 patients with type IIa hypercholesterolemia randomized to receive in a double-blind fashion simvastatin (20 mg/d) or placebo for 3 months. The urinary excretion of 11-dehydro-TXB 2 , largely a reflection of platelet TXA 2 production in vivo, was measured by a previously validated radioimmunoassay technique. Blood lipid levels and urinary 11-dehydro-TXB 2 excretion were significantly ( P <.001) reduced by simvastatin. In contrast, placebo-treated patients did not show any statistically significant changes in either blood lipids or 11-dehydro-TXB 2 excretion. The reduction in 11-dehydro-TXB 2 associated with simvastatin was correlated with the reduction in total cholesterol ( r =.81, P <.0001), LDL cholesterol ( r =.79, P <.0001), and apolipoprotein B ( r =.76, P <.0001) levels. Platelets from patients with type IIa hypercholesterolemia required significantly ( P <.01) more collagen and ADP to aggregate and synthesized less TXB 2 in response to both agonists after simvastatin therapy. Bleeding time, platelet sensitivity to Iloprost, and blood lipoprotein(a) and HDL cholesterol levels were not significantly affected by either treatment. We conclude that enhanced TXA 2 biosynthesis in type IIa hypercholesterolemia is, at least in part, dependent on abnormal cholesterol levels and/or other simvastatin-sensitive mechanisms affecting platelet function.

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Tài liệu tham khảo

Ross R. The pathogenesis of atherosclerosis. In: Braunwald E ed. Heart Disease . Philadelphia Pa: WB Saunders Co; 1988:1135-1352.

10.1055/s-0038-1657206

10.1016/S0140-6736(79)90101-6

10.1161/01.ATV.6.2.203

10.1016/0049-3848(88)90318-0

10.1056/NEJM198001033020102

Tremoli E Colli S Maderna P Baldassarre D Di Minno G. Hypercholesterolemia and platelets. Semin Thromb Hemost . 1993;19: 115-121.

10.1161/circ.85.5.1572035

10.1161/circ.45.2.501

10.1016/0049-3848(80)90066-3

Bologna M Carlucci G Biordi L Mazzeo P Iannarrelli R. HPLC determination of simvastatin and L 654 969 in plasma after oral administration of simvastatin to hypercholesterolemic patients. Int J Immunopathol Pharmacol . In press.

1974, Chem Klin Biochem, 12, 226

Wahalefeld AW. Triglyceride determination after enzymatic hydrolysis. In: Bergmeyer HU ed. Methods of Enzymatic Analysis . New York NY: Academic Press Inc; 1974:1831-1835.

1970, J Lipid Res, 11, 583, 10.1016/S0022-2275(20)42943-8

10.1007/BF02984927

1977, J Lipid Res, 18, 331, 10.1016/S0022-2275(20)41683-9

1980, Clin Chem, 18, 499

1989, Metabolism, 38, 1

10.1038/194927b0

10.1016/0005-2760(87)90233-5

10.1016/0304-4165(89)90051-2

Siegel S. Nonparametric Statistics for the Behavioral Sciences . New York NY: McGraw-Hill Publishing Co; 1986:184-193.

1990, Eicosanoids, 3, 67

10.1016/0021-9150(89)90036-1

1989, Eicosanoids, 2, 39

10.1016/0021-9150(89)90094-4

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Arteriosclerosis, Thrombosis, and Vascular Biology

Tập 15 Số 2

247-251

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