瘦素上调小窝蛋白-1 的表达：对动脉粥样硬化发生发展的影响。
Leptin upregulates caveolin-1 expression: implications for development of atherosclerosis.
机构信息
Division of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.
出版信息
Atherosclerosis. 2011 Aug;217(2):499-502. doi: 10.1016/j.atherosclerosis.2010.10.012. Epub 2010 Oct 16.
Abstract
OBJECTIVE
To determine the role of hyperleptinemia on caveolin-1 expression and leptin signaling.
METHODS
Endothelial cells are critical to atherosclerosis development; therefore we investigated hyperleptinemia in cultured vascular endothelial cells. Dose-dependent effect of leptin on caveolin-1 expression was determined by Western blot analysis. Also, the consequence of increased caveolin-1 expression on leptin signaling was investigated by adenovirus mediated caveolin-1 overexpression. The effect of increased caveolin-1 expression on leptin-dependent activation of ERK1/2 and eNOS was determined by Western blot analysis.
RESULTS
Leptin upregulates caveolin-1 protein expression in a dose dependent manner and increased caveolin-1 expression impairs leptin signaling.
CONCLUSIONS
Leptin increases caveolin-1 protein expression which impairs leptin signaling in vascular endothelial cells. Our study identifies an additional leptin mediated proatherogenic mechanism and a novel caveolin-1 dependent leptin feedback mechanism which may have implications for development of peripheral leptin resistance in the endothelium.
摘要
目的
确定高瘦素血症对窖蛋白-1 表达和瘦素信号的作用。
方法
内皮细胞对动脉粥样硬化的发展至关重要；因此，我们研究了培养的血管内皮细胞中的高瘦素血症。通过 Western blot 分析确定瘦素对窖蛋白-1 表达的剂量依赖性效应。此外，还通过腺病毒介导的窖蛋白-1 过表达研究了增加窖蛋白-1 表达对瘦素信号的影响。通过 Western blot 分析确定增加窖蛋白-1 表达对瘦素依赖性 ERK1/2 和 eNOS 激活的影响。
结果
瘦素呈剂量依赖性地上调窖蛋白-1 蛋白表达，增加的窖蛋白-1 表达损害瘦素信号。
结论
瘦素增加血管内皮细胞中窖蛋白-1 蛋白的表达，从而损害瘦素信号。我们的研究确定了另一种瘦素介导的促动脉粥样硬化机制和一种新的窖蛋白-1 依赖的瘦素反馈机制，这可能对内皮细胞中外周瘦素抵抗的发展有影响。
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