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.
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 (AT1) 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.
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Feng
F
Zhang
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Xingsheng
X
Ren
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Mingxia
M
Zhao
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Bing
B
Zhou
Key Laboratory of Cardiovascular Disease and Molecular Intervention, Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Ying
Y
Han
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