Apelin-13 treatment enhances the stability of atherosclerotic plaques
Apelin-13 treatment enhances the stability of atherosclerotic plaques
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DOI：
10.1111/eci.12891
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发表时间：
2018-03-01
影响因子：
5.5
通讯作者：
da Silva, Rafaela F.
中科院分区：
文献类型：
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作者：
Fraga-Silva, Rodrigo A.;Seeman, Hugo;da Silva, Rafaela F.
apelin是一种调节心血管功能的内源性肽能系统。近年来的研究指出，尖蛋白在动脉粥样硬化的发生发展中起着重要的作用；然而，这些报告揭示了相互矛盾的数据，迄今为止，很难准确界定有益或有害的作用。为了更好地了解apelin在动脉粥样硬化中的作用，我们旨在研究apelin-13对动脉粥样硬化斑块组成的治疗作用。设计型载脂蛋白E基因缺失小鼠饲喂西式饮食11周。通过剪切应力调节装置诱导颈动脉粥样硬化斑块的形成，该装置使同一血管暴露于不同的剪切应力模式，从而形成不同成分的斑块。小鼠用apelin-13 (2 mg kg（-1) day(-1)）或载药治疗最后3周。结果apelin -13处理未改变颈动脉低剪切应力和振荡剪切应力诱导斑块的脂质含量。然而，apelin-13通过增加斑块内胶原含量和降低MMP-9的表达，极大地改善了斑块的稳定性。此外，apelin-13降低炎症细胞（中性粒细胞和巨噬细胞）的浸润和斑块内活性氧含量。有趣的是，apelin-13治疗降低了总胆固醇、低密度脂蛋白水平和游离脂肪酸血清水平，而HDL、甘油三酯血清水平没有显著变化。结论sapelin -13治疗3周未改变斑块大小，但明显增强了动脉粥样硬化斑块的稳定表型，改善了血脂水平。这些结果表明，激活apelin系统可降低斑块易损性。
BackgroundApelin is an endogenous peptidergic system which modulates cardiovascular function. Recent studies pointed out a fundamental contribution of apelin on atherosclerosis development; however, such reports revealed contradictory data, and to date, it is difficult to accurately define a beneficial or deleterious role. To better understand apelin function on atherosclerosis, we aimed to investigate apelin-13 treatment effects on atherosclerotic plaques composition.DesignApolipoprotein E gene-deleted mice were fed on Western-type diet for 11 weeks. Atherosclerotic plaque formation was induced in the carotid artery by a shear stress modifier device, which exposes the same vessel to distinct patterns of shear stress enabling the formation of plaques with different composition. Mice were treated with apelin-13 (2 mg kg(-1) day(-1)) or vehicle for the last 3 weeks.ResultsApelin-13 treatment did not alter the lipid content of low shear stress- and oscillatory shear stress-induced plaques in the carotid. However, apelin-13 greatly ameliorated plaque stability by increasing intraplaque collagen content and reducing MMP-9 expression. Furthermore, apelin-13 decreased the infiltration of inflammatory cells (neutrophil and macrophage) and intraplaque reactive oxygen species content. Interestingly, apelin-13 treatment reduced total cholesterol, LDL levels and free fatty acid serum levels, while HDL, triglycerides serum levels were not significantly changed.ConclusionsApelin-13 treatment for 3 weeks did not alter the lesion size, but it significantly enhanced the stable phenotype of atherosclerotic plaques and improved serum lipid profile. These results indicate that activation of apelin system decreases plaque vulnerability.