Notarbartolo A, Davì G, Averna M, Barbagallo C M, Ganci A, Giammarresi C, La Placa F P, Patrono C
Department of Medicine, University of Palermo, Italy.
Arterioscler Thromb Vasc Biol. 1995 Feb;15(2):247-51. doi: 10.1161/01.atv.15.2.247.
Thromboxane A2 (TXA2) 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 TXB2 production ex vivo, we investigated TXA2 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-TXB2, largely a reflection of platelet TXA2 production in vivo, was measured by a previously validated radioimmunoassay technique. Blood lipid levels and urinary 11-dehydro-TXB2 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-TXB2 excretion. The reduction in 11-dehydro-TXB2 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 TXB2 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 TXA2 biosynthesis in type IIa hypercholesterolemia is, at least in part, dependent on abnormal cholesterol levels and/or other simvastatin-sensitive mechanisms affecting platelet function.
多数IIa型高胆固醇血症患者的血栓素A2（TXA2）生物合成增强。由于辛伐他汀（一种3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂）此前已被证明可在体外降低血小板聚集和TXB2生成，我们对24例IIa型高胆固醇血症患者进行了研究，这些患者被随机双盲给予辛伐他汀（20mg/d）或安慰剂，为期3个月。采用先前验证的放射免疫分析技术测定11-脱氢-TXB2的尿排泄量，其在很大程度上反映体内血小板TXA2的生成。辛伐他汀显著降低了血脂水平和尿11-脱氢-TXB2排泄量（P <.001）。相比之下，接受安慰剂治疗的患者血脂或11-脱氢-TXB2排泄量均未出现任何具有统计学意义的变化。与辛伐他汀相关的11-脱氢-TXB2降低与总胆固醇（r =.81，P <.0001）、低密度脂蛋白胆固醇（r =.79，P <.0001）和载脂蛋白B（r =.76，P <.0001）水平的降低相关。IIa型高胆固醇血症患者的血小板在辛伐他汀治疗后，聚集时需要显著更多（P <.01）的胶原蛋白和二磷酸腺苷，并且对两种激动剂的反应中合成的TXB2更少。出血时间、血小板对伊洛前列素的敏感性以及血液脂蛋白(a)和高密度脂蛋白胆固醇水平均未受到任何一种治疗的显著影响。我们得出结论，IIa型高胆固醇血症中增强的TXA
