Losartan inhibits EGFR transactivation in vascular smooth muscle cells

Background/aim: Angiotensin II (Ang II)-induced molecular signaling pathways play a significant role in the progression ofcardiovascular diseases, including hypertension and atherosclerosis. In addition to the well-known effects of Ang II, it may activateepidermal growth factor receptor (EGFR) in a process known as transactivation, which contributes to vascular pathologies. The aimof this study was to determine whether losartan could reduce EGFR transactivation induced by Ang II. Additionally, we evaluated theroles of heparin-binding epidermal-like growth factor (HB-EGF) and matrix metalloproteinases (MMPs) in Ang II-induced EGFRtransactivation.Materials and methods: Vascular smooth muscle cells were isolated from a rat aorta and grown in primary culture. Ang II-inducedEGFR phosphorylation (tyrosine 1068) and ERK1/2 MAPK phosphorylation (threonine 202 and tyrosine 204) were evaluated bywestern blotting.Results: Ang II induced EGFR phosphorylation through the Ang II type I receptor (P < 0.05). The transactivation process was inhibitedby losartan and mediated by HB-EGF and MMPs. Ang II transactivates EGFR in an AT1R-dependent manner.Conclusion: The results of this study show that losartan, a widely used antihypertensive agent, can suppress EGFR phosphorylation(Y1068) upon Ang II stimulation in vascular smooth muscle cells. EGFR inhibition is a candidate therapy for combating cardiovasculardiseases such as hypertension and atherosclerosis.

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