Nour-Eldine Wared, Ghantous Crystal M, Zibara Kazem, Dib Leila, Issaa Hawraa, Itani Hana A, El-Zein Nabil, Zeidan Asad
Cardiovascular Physiology Lab, Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of BeirutBeirut, Lebanon; ER045, Laboratory of Stem Cells, Department of Biology, Faculty of Sciences, The Lebanese UniversityBeirut, Lebanon.
Cardiovascular Physiology Lab, Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut Beirut, Lebanon.
Front Pharmacol. 2016 Apr 7;7:86. doi: 10.3389/fphar.2016.00086. eCollection 2016.
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.
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 p22(phox) mRNA expression were inhibited by APN and NO. Both compounds failed to inhibit Nox1 and p47(phox) expression.
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.
脂联素（APN）是一种脂肪细胞因子，对心脏重塑具有保护作用，而血管紧张素II（Ang II）可诱发高血压和血管重塑。APN在高血压期间对血管系统的潜在保护作用尚未完全阐明。在此，我们评估APN在血管壁对Ang II的生理反应中的保护作用的分子机制。
使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信号通路、肌动蛋白细胞骨架重塑和活性氧（ROS）是否介导了APN的抗肥大作用。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激活和血管张力产生的显著增加有关，而APN和SNAP可预防这种情况。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，Ang II处理24小时可增加F-肌动蛋白与G-肌动蛋白的比率，而SNAP可抑制这种作用。APN和NO可抑制Ang II诱导的ROS形成和p22(phox) mRNA表达上调。这两种化合物均未能抑制Nox1和p47(phox)表达。
我们的结果表明，APN的抗肥大作用部分归因于对RhoA/ROCK信号通路和ROS形成的NO依赖性抑制。
