CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart
CD36 mediates the cardiovascular action of growth hormone-releasing peptides in the heart
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DOI：
10.1161/01.res.0000016164.02525.b4
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发表时间：
2002-05-03
影响因子：
20.1
通讯作者：
Ong, H
中科院分区：
文献类型：
--
作者：
Bodart, V;Febbraio, M;Ong, H
生长激素释放肽（GHRPs）被认为是一种有效的生长激素分泌剂，其作用是由生长激素受体介导的。从垂体文库中克隆的G蛋白偶联受体。Hexarelin是GHRP家族的一种六肽，据报道具有心血管活性。为了确定介导这种活性的分子靶点，用放射性光激活的hexarelin衍生物标记大鼠心膜，并使用凝集素亲和层析和制备凝胶电泳纯化。鉴定出M， 84000的结合蛋白。去糖基化蛋白的n端序列测定与大鼠CD36相同。一种在心肌细胞和微血管内皮细胞中表达的多功能糖蛋白。在灌注的心脏中，经hexarelin激活CD36可引起冠状动脉灌注压以剂量依赖的方式增加。CD36缺失小鼠的心脏和CD36基因缺陷自发性高血压大鼠的心脏缺乏这种作用。通过免疫印迹和与hexarelin的共价结合评估，冠状动脉血管收缩反应与CD36的表达相关。这些数据提示CD36可能介导高胆固醇血症和动脉粥样硬化中出现的冠状动脉痉挛。
Growth hormone-releasing peptides (GHRPs) are known as potent growth hormone secretagogues whose actions are mediated by the ghrelin receptor. a G protein-coupled receptor cloned from pituitary libraries. Hexarelin, a hexapeptide of the GHRP family, has reported cardiovascular activity. To identify the molecular target mediating this activity, rat cardiac membranes were labeled with a radioactive photoactivatable derivative of hexarelin and purified using lectin affinity chromatography and preparative gel electrophoresis. A binding protein of M, 84 000 was identified. The N-terminal sequence determination of the deglycosylated protein was identical to rat CD36. a multifunctional glycoprotein, which was expressed in cardiomyocytes and microvascular endothelial cells. Activation of CD36 in perfused hearts by hexarelin was shown to elicit an increase in coronary perfusion pressure in a dose-dependent manner. This effect was lacking in hearts from CD36-null mice and hearts from spontaneous hypertensive rats genetically deficient in CD36. The coronary vasoconstrictive response correlated with expression of CD36 as assessed by immunoblotting and covalent binding with hexarelin. These data suggest that CD36 may mediate the coronary vasospasm seen in hypercholesterolemia and atherosclerosis.