Abstract

Leptin, an adipocyte-derived hormone, is involved in the regulation of body weight and is associated with obesity-related complications, notably cardiovascular disease (CVD). A putative link between obesity and CVD could be induction of plasminogen activator inhibitor-1 (PAI-1) synthesis by leptin. In this study, we hypothesized that the beneficial effect of the angiotensin-converting enzyme inhibitor (ACE_i) enalapril on PAI-1 levels is mediated by effects on leptin levels. The association between leptin and components of the fibrinolytic system was evaluated in a non-prespecified post hoc analysis of a placebo-controlled randomized, double-blind trial where the effect of the ACE_i enalapril on fibrinolysis was tested. A total of 46 men and 37 women were randomized to treatment with enalapril or placebo after (median 12 months) an uncomplicated myocardial infarction. At baseline, the participants were stable and had no signs of congestive heart failure. Leptin and fibrinolytic variables (mass concentrations of PAI-1, tissue plasminogen activator (tPA) and tPA–PAI complex) were measured at baseline, and after 10 days, 6 months and 12 months. Enalapril treatment did not change leptin levels, which increased significantly during 1 year of follow-up (p = .007). Changes in leptin levels were strongly associated with changes of tPA mass (p = .001), tPA–PAI complex (p = .003) and of PAI-1 (p = .006) in men, but not in women. Leptin levels are not influenced by treatment with an ACE_i. In contrast, leptin associates strongly with changes in fibrinolytic variables notably with a sex difference, which could be of importance for obesity-related CVD.

摘要

瘦素是一种来自脂肪细胞的激素，它参与体重的调节，并与肥胖相关的并发症有关，尤其是心血管疾病（CVD）。肥胖与CVD之间的推测联系可能是瘦素诱导了纤溶酶原激活物抑制剂1（PAI-1）的合成。在这项研究中，我们假设血管紧张素转化酶抑制剂（ACE _i）依那普利对PAI-1水平的有益作用是由对瘦素水平的影响介导的。瘦素和纤维蛋白溶解系统的组件之间的关联在非预先指定的评价事后安慰剂对照随机化，双盲试验的分析，其中所述ACE的效果_我依那普利对纤维蛋白溶解进行了测试。在无并发症的心肌梗塞后（中位数为12个月），总共有46名男性和37名女性被随机分配接受依那普利或安慰剂治疗。基线时，参与者稳定，没有充血性心力衰竭的迹象。在基线，10天，6个月和12个月后测量瘦素和纤溶变量（PAI-1的质量浓度，组织纤溶酶原激活物（tPA）和tPA-PAI复合物）。依那普利治疗不会改变瘦素水平，瘦素水平在随访的1年中显着增加（p  = .007）。瘦素水平的变化与tPA质量（p  = .001），tPA–PAI复合物（p  = .003）和PAI-1（p = .006），但男性没有。瘦素水平不受ACE _i治疗的影响。相反，瘦素与纤溶变量的变化密切相关，特别是与性别差异有关，这对于肥胖相关的CVD可能很重要。