Angiotensin-(1-7) Attenuates Angiotensin II-Induced ICAM-1, VCAM-1, and MCP-1 Expression via the MAS Receptor Through Suppression of P38 and NF-kappa B Pathways in HUVECs

作者：Liang, Bin; Wang, Xin; Zhang, Nana; Yang, Huiyu; Bai, Rui; Liu, Ming; Bian, Yunfei; Xiao, Chuanshi; Yang, Zhiming^*

来源：Cellular Physiology and Biochemistry, 2015, 35(6): 2472-2482.

DOI：10.1159/000374047

• Atherosclerosis
• Angiotensin-(1-7)
• Angiotensin II
• ICAM-1
• VCAM-1
• MCP-1

Background/Aims: Atherosclerosis is a chronic inflammatory disease. Intracellular adhesion molecule-1 (ICAM-1), vascular cellular adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) play important roles in inflammatory processes. P38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B signaling regulate ICAM-1, VCAM-1, and MCP-1 expression. Angiotensin (Ang) II upregulates ICAM-1, VCAM-1, and MCP-1 expression through the P38 MAPK and NF-kappa B pathways. Ang-(1-7) may oppose the actions of Ang II. We investigated whether Ang-(1-7) prevents Ang II-induced ICAM-1, VCAM-1, and MCP-1 expression in human umbilical vein endothelial cells (HUVECs). Methods: ICAM-1, VCAM-1, and MCP-1 expression was estimated by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA); P38, NF-kappa B, and p-I kappa B-alpha expression was estimated by western blotting. Results: Ang-(1-7) inhibited Ang II-induced ICAM-1, VCAM-1, and MCP-1 expression and secretion in HUVECs. Ang II sharply increased P38 MAPK phosphorylation, which was inhibited by pretreatment with Ang-(1-7). Moreover, Ang(1-7) significantly inhibited Ang II-induced I kappa B-alpha phosphorylation and NF-kappa B P65 nuclear translocation. The MAS receptor antagonist A-779 abolished the suppressive effects of Ang-(1-7). Conclusion: Ang-(1-7) attenuates Ang II-induced ICAM-1, VCAM-1, and MCP-1 expression via the MAs receptor by suppressing the P38 and NF-kappa B pathways in HUVECs. Ang-(1-7) might delay the progression of inflammatory diseases, including atherosclerosis.

• 出版日期2015
• 单位山西医科大学; 山西医科大学第二医院