Mussoni L, Mannucci L, Sirtori M, Camera M, Maderna P, Sironi L, Tremoli E
E. Grossi Paoletti Center, University of Milan, Italy.
Arterioscler Thromb. 1992 Jan;12(1):19-27. doi: 10.1161/01.atv.12.1.19.
A relation between elevated triglyceride (TG) levels and alterations of the fibrinolytic system has been recognized in studies of patients with coronary heart disease. In this investigation, the total fibrinolytic activity and the levels of specific components of the fibrinolytic system were evaluated in plasma samples from a highly selected group of patients with type IV hyperlipoproteinemia before and after a dietary treatment aimed at reducing TG levels. The fibrinolytic response of type IV patients was comparable to that of normolipidemic subjects, whereas tissue-type plasminogen activator antigen levels before and after venous occlusion (p less than 0.01) and resting plasminogen activator inhibitor-1 (PAI-1) antigen (p less than 0.01) and activity (p less than 0.01) were significantly higher in hypertriglyceridemic subjects compared with controls. After dietary treatment, a 22% reduction in TG levels was attained in type IV patients, with no appreciable modification of fibrinolytic parameters. The analysis of the single-patient data revealed a tendency toward normalization of PAI-1 levels only in those patients who showed a TG reduction greater than or equal to 20%. Very low density lipoproteins (VLDLs) from both normal and type IV patients concentration-dependently stimulated PAI-1 release by endothelial cells and HepG2 cells, with the effect of VLDL from type IV patients being more pronounced on HepG2 cells. The release of PAI-1 induced by VLDL in competent cells may thus account for the elevated levels of this antifibrinolytic protein that occur in hypertriglyceridemic patients.
在冠心病患者的研究中,已认识到甘油三酯(TG)水平升高与纤溶系统改变之间的关系。在本研究中,对一组经过高度筛选的IV型高脂蛋白血症患者在旨在降低TG水平的饮食治疗前后的血浆样本,评估了纤溶系统的总纤溶活性和特定成分水平。IV型患者的纤溶反应与血脂正常的受试者相当,而与对照组相比,高甘油三酯血症患者静脉闭塞前后的组织型纤溶酶原激活物抗原水平(p<0.01)、静息状态下纤溶酶原激活物抑制剂-1(PAI-1)抗原(p<0.01)和活性(p<0.01)显著更高。饮食治疗后,IV型患者的TG水平降低了22%,纤溶参数无明显改变。对单例患者数据的分析显示,只有那些TG降低大于或等于20%的患者,其PAI-1水平有趋于正常的倾向。来自正常人和IV型患者的极低密度脂蛋白(VLDL)均浓度依赖性地刺激内皮细胞和HepG2细胞释放PAI-1,IV型患者的VLDL对HepG2细胞的作用更明显。因此,VLDL在有反应的细胞中诱导的PAI-1释放可能解释了高甘油三酯血症患者中这种抗纤溶蛋白水平升高的现象。