Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity
Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity
复制标题
DOI：
10.1172/jci200113143
复制
发表时间：
2001-11-01
影响因子：
15.9
通讯作者：
Loskutoff, DJ
中科院分区：
文献类型：
--
作者：
Konstantinides, S;Schäfer, K;Loskutoff, DJ
肥胖与心血管疾病发病率和死亡率增加以及饱腹感因子瘦素循环水平升高相关。这项研究为瘦素与肥胖个体血栓并发症风险之间的直接联系提供了证据。例如，尽管动脉损伤在瘦和肥胖（ob/ob）小鼠中引起血栓形成，但是在ob/ob小鼠中完成血栓闭塞的时间显著延迟，并且形成的血栓不稳定并且经常栓塞。ob/ob小鼠缺乏瘦素，并且在损伤前向这些小鼠腹膜内施用瘦素通过缩短闭塞时间、稳定血栓和降低通畅率来恢复瘦小鼠的表型。当瘦素受体缺陷型肥胖（db/db）小鼠受伤时形成的血栓也是不稳定的。然而，在这种情况下，瘦素没有效果。血小板表达瘦素受体，瘦素增强ob/ob小鼠而非db/db小鼠的血小板对已知激动剂的反应的聚集。这些结果揭示了瘦素对血小板功能和止血的一种新的受体依赖性作用，并为肥胖个体心血管并发症的分子基础提供了新的见解。结果表明，这些血栓形成前的属性时，应考虑开发基于瘦素的治疗策略。
Obesity is associated with increased cardiovascular morbidity and mortality and with elevated circulating levels of the satiety factor leptin. This study provides evidence for a direct link between leptin and the risk for thrombotic complications in obese individuals. For example, although arterial injury provokes thrombosis in both lean and obese (ob/ob) mice, the time to complete thrombotic occlusion is significantly delayed in the ob/ob mice, and the thrombi formed are unstable and frequently embolize. The ob/ob mice lack leptin, and intraperitoneal administration of leptin to these mice before injury restores the phenotype of lean mice by shortening the time to occlusion, stabilizing the thrombi, and decreasing the patency rate. The thrombi that form when leptin receptor-deficient obese (db/db) mice are injured also are unstable. However, in this instance, leptin has no effect. Platelets express the leptin receptor, and leptin potentiates the aggregation of platelets from ob/ob but not db/db mice in response to known agonists. These results reveal a novel receptor-dependent effect of leptin on platelet function and hemostasis and provide new insights into the molecular basis of cardiovascular complications in obese individuals. The results suggest that these prothrombotic properties should be considered when developing therapeutic strategies based on leptin.