The investigation of the relationship between at1r activation and egfr transactivation in vascular smooth muscle cells induced by epidermal growth factor and angiotensin II

Ang II stimulated signal transduction mechanisms and the role of Ang II in vascular pathologies has been explored for years. Ang II contributes to development of cardiovascular diseases including, hypertension and atherosclerosis by enhancing mitogenic activity, proliferation, hyperplasia, inflammatory mediators production, and stimulating migration of VSMCs. It is known well Ang II and, in a similar way, EGF ligand induces signaling pathways such as ERK1/2 which may results in cell growth, apoptosis, inflammation and migration of VSMCs. The present study was conducted to enlighten Ang II-induced EGFR transactivation event and possible mechanisms that links AT1R to EGFR. In our study, Ang II- or EGF-induced ERK1/2 and EGFR-Tyr1068 phosphorylations were investigated by using different inhibitors in VSMCs. Analysis of experiments? data shows that treatment of VSMCs with Ang II or EGF induces ERK1/2 and EGFR phosphorylation. Ang II-induced ERK1/2 phosphorylation is a downstream event of EGFR transactivation. Ang II transactivates EGFR through AT1R leading to ERK1/2 activation. EGFR transactivation is indispensable for ERK1/2 phosphorylation caused by Ang II. Ang II-induced EGFR transactivation is mediated by release of HB-EGF. Ang II, but not EGF, causes ERK1/2 activation by increasing MMP activity. In conclusion, the results of our study indicates that Ang II leads to EGFR transactivation and subsequent ERK1/2 pathway activation in VSMCs. It may be clinically possible to use EGFR inhibitor(s) as a drug to abrogate the pathophysiological effects of Ang II in cardiovascular diseases after further studies on this topic soon.