阿托伐他汀对高胆固醇血症患者不同纤溶机制的影响。

Effect of atorvastatin on different fibrinolyis mechanisms in hypercholesterolemic subjects.

作者信息

Bruni F, Pasqui A L, Pastorelli M, Bova G, Di Renzo M, Cercigani M, Leo A, Auteri A, Puccetti L

机构信息

Department of Clinical Medicine and Immunological Sciences, Internal Medicine Division, Center for Metabolic Diseases and Atherosclerosis, University of Siena, Policlinico Le Scotte, V.le Bracci, 53100 Siena, Italy.

出版信息

Int J Cardiol. 2004 Jun;95(2-3):269-74. doi: 10.1016/j.ijcard.2003.08.003.

DOI:10.1016/j.ijcard.2003.08.003

PMID:15193831

Abstract

BACKGROUND

Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins) reduce cardiovascular events by cholesterol lowering as well as non-lipid related actions. Among them, the modulation of fibrinolysis could play a relevant role in vascular protection. Atorvastatin is able of reducing platelet activity and thrombin generation before low-density lipoprotein cholesterol (LDL-C) decrease in hypercholesterolemic subjects in which coagulation and fibrinolysis are linked by the activation of thrombin activable fibrinolysis inhibitor (TAFI). The aim of our study was to evaluate whether atorvastatin could modulate fibrinolysis by interactions with endothelial mechanisms and thrombin generation.

METHODS

Forty-four pure hypercholesterolemic subjects (26 M, 18 F, mean age 52.7+/-13.7, LDL-C 194.8+/-9.3t mg/dl) were evaluated for plasmin-antiplasmin complexes (PAP), tissue-plasminogen acivator (t-PA) and its inhibitor (PAI-1) (ELISA), TAFI activity (HPLC), platelet P-selectin (P-sel) (cytofluorymetric detection), platelet-dependent thrombin generation (PDTG, coagulative-chromogenic method) and lipid profile at baseline and after 7, 14, 28 and 90 days of atorvastatin (10 mg/die) treatment.

RESULTS

PAP were significantly reduced at baseline in hypercholesterolemic versus control subjects (P<0.05) and were related to P-sel (P<0.01), PDTG (P<0.01) and its inhibitor (PAI-1) after venous occlusion (VO) (P<0.05). Atorvastatin induced a significant increase of PAP at T(2) related to modifications of P-sel (P<0.01) and PDTG (P<0.01) before significant LDL-C reduction (P=0.132). PAI-1 was significantly changed at T(3) with relation to LDL-C (P<0.01), Von Willebrand factor (VWF) (P<0.01) and sE-sel (P<0.05).

CONCLUSIONS

The profibrinolytic activity of atorvastatin in hypercholesterolemic subjects is related, initially, to the positive effects exerted on platelet function and thrombin generation which can modulate fibrinolysis by TAFI activity.

摘要

背景

羟甲基戊二酰辅酶A还原酶抑制剂（他汀类药物）通过降低胆固醇以及非脂质相关作用来减少心血管事件。其中，纤维蛋白溶解的调节可能在血管保护中发挥重要作用。阿托伐他汀能够在低密度脂蛋白胆固醇（LDL-C）降低之前，降低高胆固醇血症患者的血小板活性和凝血酶生成，在这些患者中，凝血和纤维蛋白溶解通过凝血酶激活的纤维蛋白溶解抑制剂（TAFI）的激活而相互关联。我们研究的目的是评估阿托伐他汀是否能通过与内皮机制和凝血酶生成的相互作用来调节纤维蛋白溶解。

方法

对44名单纯高胆固醇血症患者（26名男性，18名女性，平均年龄52.7±13.7岁，LDL-C 194.8±9.3mg/dl）进行评估，检测其纤溶酶 - 抗纤溶酶复合物（PAP）、组织纤溶酶原激活物（t-PA）及其抑制剂（PAI-1）（酶联免疫吸附测定法）、TAFI活性（高效液相色谱法）、血小板P-选择素（P-sel）（细胞荧光检测法）、血小板依赖性凝血酶生成（PDTG，凝固 - 发色法）以及在基线时和阿托伐他汀（10mg/天）治疗7、14、28和90天后的血脂谱。

结果

与对照组相比，高胆固醇血症患者基线时PAP显著降低（P<0.05），并且与静脉闭塞（VO）后的P-sel（P<0.01）、PDTG（P<0.01）及其抑制剂（PAI-1）相关（P<0.05）。在LDL-C显著降低之前（P = 0.132），阿托伐他汀在T(2)时导致PAP显著增加，这与P-sel（P<0.01）和PDTG（P<0.01）的改变有关。PAI-1在T(3)时与LDL-C（P<0.01）、血管性血友病因子（VWF）（P<0.01）和可溶性E-选择素（sE-sel）（P<0.05）显著相关。