Requirement of apelin-apelin receptor system for oxidative stress-linked atherosclerosis
Requirement of apelin-apelin receptor system for oxidative stress-linked atherosclerosis
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DOI：
10.2353/ajpath.2007.070471
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发表时间：
2007-11-01
影响因子：
6
通讯作者：
Umemura, Satoshi
中科院分区：
文献类型：
--
作者：
Hashimoto, Tatsuo;Kihara, Minoru;Umemura, Satoshi
最近鉴定的内源性肽爱帕琳及其特异性爱帕琳受体（APJ）目前被认为是血管组织中的潜在调节剂。以前，我们报道了apelin介导肌球蛋白轻链磷酸化和血管收缩。在这项研究中，apelin-APJ系统的生理作用进行了研究动脉粥样硬化。在不受胆固醇水平影响的情况下，与APJ（+/+）ApoE（-/-）小鼠相比，饲喂高胆固醇饲料的APJ和载脂蛋白E双敲除（APJ（-/-）ApoE（-/-））小鼠的动脉粥样硬化病变显著减少。使用平滑肌α-肌动蛋白抗体对平滑肌细胞进行免疫组织化学检测，结果显示，在喂食高胆固醇饮食的APJ（+/+）ApoE（-/-）小鼠的病变中，这些细胞的染色大大减少。与饲喂标准正常饮食的APJ（+/+）ApoE（-/-）小鼠相比，APJ（-/-）ApoE（-/-）小鼠血管产生的超氧自由基和烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚基的表达减少。在血管平滑肌细胞中，爱帕琳诱导烟酰胺腺嘌呤二核苷酸磷酸氧化酶亚单位表达。Apelin还诱导血管平滑肌细胞增殖，这是抑制超氧化物歧化酶或二苯碘鎓。apelin-APJ系统是血管组织中氧化应激的介质，因此我们认为它是高胆固醇饮食条件下动脉粥样硬化形成的关键因素。APJ缺乏可预防氧化应激相关动脉粥样硬化。
The recently identified endogenous peptide apelin and its specific apelin receptor (APJ) are currently being considered as potential regulators in vascular tissue. Previously, we reported apelin mediates phosphorylation of myosin light chain and elicits vasoconstriction in vascular smooth muscle. In this study, physiological roles of the apelin-APJ system were investigated on atherosclerosis. In APJ and apolipoprotein E double-knockout (APJ(-/-)ApoE(-/-)) mice fed a high-cholesterol diet, atherosclerotic lesions were dramatically reduced when compared with APJ(+/+) ApoE(-/-) mice, in the absence of an effect of cholesterol levels. Immunohistochemical detection of smooth muscle cells, using a smooth muscle a-actin antibody, showed greatly reduced staining for these cells in lesions of APJ(+/+)ApoE(-/-) mice fed a highcholesterol diet. Vascular production of superoxide radicals and the expression of nicotinamide-adenine dinucleotide phosphate oxidase subunits were decreased in APJ(-/-)ApoE(-/-) mice compared with APJ(+/+)ApoE(-/-) mice fed a standard normal diet. in vascular smooth muscle cells, apelin induced nicotinamide-adenine dinucleotide phosphate oxidase subunit expression. Apelin also induced vascular smooth muscle cell proliferation, which was inhibited by superoxide dismutase or diphenylene iodonium. The apelin-APJ system is a mediator of oxidative stress in vascular tissue, and thus we propose it to be a critical factor in atherogenesis under high-cholesterol dietary conditions. APJ deficiency is preventative against oxidative stresslinked atherosclerosis.