Angiotensin-(1-7) abrogates angiotensin II-induced proliferation, migration and inflammation in VSMCs through inactivation of ROS-mediated PI3K/Akt and MAPK/ERK signaling pathways

作者：Zhang, Feng; Ren, Xingsheng; Zhao, Mingxia; Zhou, Bing; Han, Ying^*

来源：Scientific Reports, 2016, 6(1): 34621.

DOI：10.1038/srep34621

• SMOOTH-MUSCLE-CELL
• CONVERTING ENZYME 2
• NADPH OXIDASE
• ANG-II
• RECEPTOR
• COUNTERACTS
• HYPERTENSION
• ACTIVATION
• MECHANISMS
• INHIBITION

The proliferation, migration and inflammation of vascular smooth muscle cells (VSMCs) contribute to the pathogenesis and progression of several cardiovascular diseases such as atherosclerosis and hypertension. Angiotensin (Ang)-(1-7) and Ang II are identified to be involved in regulating cardiovascular activity. The present study is designed to determine the interaction between Ang-(1-7) and Ang II on VSMCs proliferation, migration and inflammation as well as their underlying mechanisms. We found that Ang-(1-7) significantly suppressed the positive effects of Ang II on VSMCs proliferation, migration and inflammation, as well as on induction of the phosphorylation of Akt and ERK1/2 and increase of superoxide anion level and NAD(P) H oxidase activity in VSMCs, whereas Ang-(1-7) alone had no significant effects. This inhibitory effects of Ang-(1-7) were abolished by Mas receptor antagonist A-779. In addition, Ang II type 1 (AT(1)) receptor antagonist losartan, but not A-779, abolished Ang II induced VSMCs proliferation, migration and inflammation responses. Furthermore, superoxide anion scavenger N-acetyl-L-cysteine (NAC) or NAD(P) H oxidase inhibitor apocynin inhibited Ang II-induced activation of Akt and ERK1/2 signaling. These results indicate that Ang-(1-7) antagonizes the Ang II-induced VSMC proliferation, migration and inflammation through activation of Mas receptor and then suppression of ROS-dependent PI3K/Akt and MAPK/ERK signaling pathways.

• 出版日期2016-9-30
• 单位南京医科大学