Deletion of the EGF receptor in vascular smooth muscle cells prevents chronic angiotensin II-induced arterial wall stiffening and media thickening.

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In vivo vascular smooth muscle cell (VSMC) EGF receptor (EGFR) contributes to acute angiotensin II (AII) effects on vascular tone and blood pressure. The ubiquitously expressed EGFR has been implicated in vascular remodelling preceding end-organ damage by pharmacological inhibition, and AII signalling in cultured vascular cells is partly EGFR-dependent. However, the role of VSMC-EGFR invivo during AII-induced pathophysiological processes is not known. This study assesses the invivo relevance of VSMC-EGFR during chronic AII challenge without further stressors, using a mouse model with inducible, VSMC-specific EGFR knock out (VSMC-EGFR-KO). In these mice functional and structural vascular, renal and cardiac effects or biomarkers were investigated invivo and exvivo. Vascular smooth muscle cell-EGFR-KO prevented AII-induced media hypertrophy of mesenteric arteries, renal arterioles and the aorta, VSMC ERK1/2-phosphorylation as well as the impairment of vascular compliance. Furthermore, induction of vascular fibrosis, creatinineamia, renal interstitial fibrosis as well as the increase in fractional water excretion was prevented. AII-induced increase in systolic blood pressure was mitigated. By contrast, endothelial dysfunction, induction of vascular inflammatory marker mRNA and albuminuria were not inhibited. Cardiac and cardiomyocyte hypertrophy were also not prevented by VSMC-EGFR-KO. Vascular smooth muscle cell-EGFRs are relevant for pathological AII action invivo. Our data show invivo and exvivo the necessity of VSMC-EGFR for AII-induced structural and functional vascular remodelling, not including endothelial dysfunction. Hereby, VSMC-EGFR gains importance for complete AII-induced renal end-organ damage succeeding vascular remodelling.