Adiponectin at Physiologically Relevant Concentrations Enhances the Vasorelaxative Effect of Acetylcholine via Cav-1/AdipoR-1 Signaling.
Adiponectin at Physiologically Relevant Concentrations Enhances the Vasorelaxative Effect of Acetylcholine via Cav-1/AdipoR-1 Signaling.
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DOI：
10.1371/journal.pone.0152247
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Du Y;Li R;Lau WB;Zhao J;Lopez B;Christopher TA;Ma XL;Wang Y
临床研究已确定低脂联素血症是一个独立的高血压危险因素。脂联素（APN）可直接引起血管舒张，但所需剂量超过生理水平数倍。在目前的研究中，我们确定了生理相关的APN浓度对血管张力的影响，并研究了相关的机制。生理APN浓度单独诱导没有显着的血管舒张。有趣的是，用生理水平的APN预处理野生型小鼠睾丸显著增强乙酰胆碱（ACh）诱导的血管舒张（P<0.01），这是一种内皮依赖性和一氧化氮（NO）介导的过程。敲除脂联素受体1（AdipoR 1）或小窝蛋白-1（Cav-1，一种细胞信号传导促进分子），但不敲除脂联素受体2（AdipoR 2），可消除APN增强的ACh诱导的血管舒张。免疫印迹分析显示APN促进人内皮细胞AdipoR 1/Cav 1信号复合物的表达。用生理浓度的APN处理HUVECs引起显著的eNOS磷酸化和一氧化氮（NO）产生（P<0.01），在AdipoR 1或Cav-1的敲低中消除了这种作用。总之，这些数据首次证明生理APN水平通过AdipoR 1/Cav-1介导的信号传导诱导NO产生来增强对ACh的血管舒张反应。在生理条件下，APN起着维持血管张力的重要作用。
Clinical studies have identified hypoadiponectinemia as an independent hypertension risk factor. It is known that adiponectin (APN) can directly cause vasodilation, but the doses required exceed physiologic levels several fold. In the current study, we determine the effect of physiologically relevant APN concentrations upon vascular tone, and investigate the mechanism(s) responsible. Physiologic APN concentrations alone induced no significant vasorelaxation. Interestingly, pretreatment of wild type mouse aortae with physiologic APN levels significantly enhanced acetylcholine (ACh)-induced vasorelaxation (P<0.01), an endothelium-dependent and nitric oxide (NO)-mediated process. Knockout of adiponectin receptor 1 (AdipoR1) or caveolin-1 (Cav-1, a cell signaling facilitating molecule), but not adiponectin receptor 2 (AdipoR2) abolished APN-enhanced ACh-induced vasorelaxation. Immunoblot assay revealed APN promoted the AdipoR1/Cav1 signaling complex in human endothelial cells. Treatment of HUVECs with physiologic APN concentrations caused significant eNOS phosphorylation and nitric oxide (NO) production (P<0.01), an effect abolished in knockdown of either AdipoR1 or Cav-1. Taken together, these data demonstrate for the first time physiologic APN levels enhance the vasorelaxative response to ACh by inducing NO production through AdipoR1/Cav-1 mediated signaling. In physiologic conditions, APN plays an important function of maintaining vascular tone.