Logo image
Back
Epidermal growth factor receptor is critical for angiotensin II-mediated hypertrophy in cerebral arterioles
Journal article   Peer reviewed

Epidermal growth factor receptor is critical for angiotensin II-mediated hypertrophy in cerebral arterioles

Siu-Lung Chan, Shaikamjad Umesalma and Gary L Baumbach
Hypertension (Dallas, Tex. 1979), Vol.65(4), pp.806-812
04/2015
DOI: 10.1161/HYPERTENSIONAHA.114.04794
PMID: 25733240

View Online

Abstract

Angiotensin II (Ang II) is a major determinant of vascular remodeling in the cerebral circulation during chronic hypertension, which is an important risk factor for stroke. We examined the molecular mechanism of Ang II-mediated cerebrovascular remodeling that involves the epidermal growth factor receptor (EGFR) pathway. Mutant EGFR mice (waved-2), their heterozygous control (wild-type [WT]), and C57BL/6J mice were infused with Ang II (1000 ng kg(-1) min(-1)) or saline via osmotic minipumps for 28 days (n=8 per group). Eight of the Ang II-infused C57BL/6J mice were cotreated with AG1478 (12 mg/kg per day, IP), a specific EGFR tyrosine kinase inhibitor. Systolic arterial pressure was measured by a tail-cuff method. Pressure and diameter of cerebral arterioles were measured through an open cranial window in anesthetized mice. Cross-sectional area of the wall was determined in pressurized fixed cerebral arterioles. Expression of phosphorylated EGFR (p-EGFR), caveolin-1 (Cav-1), and c-Src was determined by western blotting and immunohistochemistry. Mutation of EGFR or AG1478 treatment did not affect Ang II-induced hypertension. Ang II increased the expression of p-EGFR in WT mice, confirming the activation of EGFR. Ang II induced hypertrophy and inward remodeling of cerebral arterioles in WT mice. Hypertrophy, but not remodeling, was prevented in waved-2 and AG1478-treated C57BL/6J mice. Ang II increased p-EGFR, Cav-1, and c-Src expression in WT but not in waved-2 or AG1478-treated C57BL/6J mice. These results suggest that Ang II-induced hypertrophy in cerebral arterioles involves EGFR-dependent signaling and may include Cav-1 and nonreceptor tyrosine kinase c-Src. This signaling pathway seems to be limited to Ang II-induced hypertrophy, but not inward remodeling, and is independent of blood pressure.
 Angiotensin II - pharmacology Animals Arterioles - metabolism Arterioles - pathology Blood Pressure - drug effects Cerebral Arteries - metabolism Cerebral Arteries - pathology Cerebrovascular Circulation Disease Models, Animal Female Gene Expression Regulation Hypertension - genetics Hypertension - metabolism Hypertension - physiopathology Immunohistochemistry Male Mice Mice, Inbred C57BL Muscle, Smooth, Vascular - metabolism Muscle, Smooth, Vascular - pathology Receptor, Epidermal Growth Factor - genetics Receptor, Epidermal Growth Factor - metabolism RNA - genetics Signal Transduction Vascular Remodeling

Details

Metrics

21 Record Views
33 Times Cited - Web of Science
Logo image