Adiponectin Attenuates Angiotensin II-Induced Vascular Smooth Muscle Cell Remodeling through Nitric Oxide and the RhoA/ROCK Pathway.
Adiponectin Attenuates Angiotensin II-Induced Vascular Smooth Muscle Cell Remodeling through Nitric Oxide and the RhoA/ROCK Pathway.
复制标题
脂联素通过一氧化氮和RhoA/ROCK途径减弱血管紧张素II诱导的血管平滑肌细胞重塑。
DOI：
10.3389/fphar.2016.00086
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发表时间：
2016
影响因子：
5.6
通讯作者：
Zeidan A
中科院分区：
文献类型：
--
作者：
Nour-Eldine W;Ghantous CM;Zibara K;Dib L;Issaa H;Itani HA;El-Zein N;Zeidan A
简介：脂联素（APN）是一种脂肪细胞因子，对心脏重塑发挥保护作用，而血管紧张素II（Ang II）则诱导高血压和血管重塑。 APN 对高血压期间脉管系统的潜在保护作用尚未完全阐明。在这里，我们评估了 APN 在血管壁对 Ang II 的生理反应中保护作用的分子机制。方法和结果：利用大鼠主动脉组织研究APN对Ang II诱导的血管重塑和肥大的影响。我们研究了一氧化氮 (NO)、RhoA/ROCK 通路、肌动蛋白细胞骨架重塑和活性氧 (ROS) 是否介导 APN 的抗肥大作用。 APN、NO 供体 S-亚硝基-N-乙酰青霉胺 (SNAP) 或 cGMP 预处理可减弱 Ang II 诱导的蛋白质合成。对 Ang II 的肥大反应与 RhoA 激活和血管力产生的显着增加有关，而 APN 和 SNAP 可以阻止这些反应。 NO 还与抑制 Ang II 诱导的丝切蛋白磷酸化有关。此外，免疫组织化学显示，24 小时 Ang II 处理增加了 F-肌动蛋白与 G-肌动蛋白的比率，而这一效应被 SNAP 抑制。 APN 和 NO 抑制 Ang II 诱导的 ROS 形成和 p22phox mRNA 表达的上调。两种化合物均未能抑制 Nox1 和 p47phox 的表达。结论：我们的结果表明 APN 的抗肥大作用部分归因于 NO 依赖性抑制 RhoA/ROCK 通路和 ROS 形成。
Introduction: Adiponectin (APN), an adipocytokine, exerts protective effects on cardiac remodeling, while angiotensin II (Ang II) induces hypertension and vascular remodeling. The potential protective role of APN on the vasculature during hypertension has not been fully elucidated yet. Here, we evaluate the molecular mechanisms of the protective role of APN in the physiological response of the vascular wall to Ang II. Methods and Results: Rat aortic tissues were used to investigate the effect of APN on Ang II-induced vascular remodeling and hypertrophy. We investigated whether nitric oxide (NO), the RhoA/ROCK pathway, actin cytoskeleton remodeling, and reactive oxygen species (ROS) mediate the anti-hypertrophic effect of APN. Ang II-induced protein synthesis was attenuated by pre-treatment with APN, NO donor S-nitroso-N-acetylpenicillamine (SNAP), or cGMP. The hypertrophic response to Ang II was associated with a significant increase in RhoA activation and vascular force production, which were prevented by APN and SNAP. NO was also associated with inhibition of Ang II-induced phosphorylation of cofilin. In addition, immunohistochemistry revealed that 24 h Ang II treatment increased the F- to G-actin ratio, an effect that was inhibited by SNAP. Ang II-induced ROS formation and upregulation of p22phox mRNA expression were inhibited by APN and NO. Both compounds failed to inhibit Nox1 and p47phox expression. Conclusion: Our results suggest that the anti-hypertrophic effects of APN are due, in part, to NO-dependent inhibition of the RhoA/ROCK pathway and ROS formation.