Recombinant leptin promotes atherosclerosis and thrombosis in apolipoprotein E-deficient mice
Recombinant leptin promotes atherosclerosis and thrombosis in apolipoprotein E-deficient mice
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DOI：
10.1161/01.atv.0000173306.47722.ec
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发表时间：
2005-08-01
影响因子：
8.7
通讯作者：
Eitzman, DT
中科院分区：
文献类型：
--
作者：
Bodary, PF;Gu, SF;Eitzman, DT
目的：瘦素在血管疾病中的直接作用仍有争议.本研究的目的是检测瘦素治疗对动脉粥样硬化倾向小鼠中动脉粥样硬化和血栓形成的影响.方法和结果--用重组瘦素（125 μ g/天IP; n = 10）或载体（n = 10）注射治疗16周龄雄性载脂蛋白E缺陷小鼠4周.瘦素治疗导致附睾脂肪减少（352 +/- 30.7 vs 621 +/- 61.5 mg; P = 0.005）和空腹胰岛素减少（0.57 +/- 0.25 vs 1.7 +/- 0.22 ng/ mL; P = 0.014）。尽管有这些代谢益处，瘦素治疗导致动脉粥样硬化增加（8.0 +/- 0.95%对5.4 +/- 0.59%病变表面覆盖率; P < 0.05）。瘦素治疗还导致血管损伤后闭塞性血栓形成时间缩短（21 +/- 2.1对34.6 +/- 5.4分钟; P = 0.045）。结论-这些研究表明，外源性瘦素促进动脉粥样硬化和血栓形成，并支持瘦素升高可能增加心血管疾病风险的概念。
Objective - The direct role of leptin in vascular disease remains controversial. The objective of this study was to examine the effects of leptin treatment on atherosclerosis and thrombosis in atherosclerotic- prone mice.Methods and Results - Sixteen- week- old, male apolipoprotein E - deficient mice were treated with injections of recombinant leptin ( 125 mu g per day IP; n = 10) or vehicle ( n = 10) for 4 weeks. Leptin treatment resulted in reduced epididymal fat ( 352 +/- 30.7 versus 621 +/- 61.5 mg; P = 0.005) and fasting insulin ( 0.57 +/- 0.25 versus 1.7 +/- 0.22 ng/ mL; P = 0.014). Despite these metabolic benefits, leptin treatment resulted in an increase in atherosclerosis ( 8.0 +/- 0.95% versus 5.4 +/- 0.59% lesion surface coverage; P < 0.05). Leptin treatment also resulted in a shortened time to occlusive thrombosis after vascular injury ( 21 +/- 2.1 versus 34.6 +/- 5.4 minutes; P = 0.045).Conclusions - These studies indicate that exogenous leptin promotes atherosclerosis and thrombosis and support the concept that elevations of leptin may increase the risk for cardiovascular disease.