| First Author | Forrester SJ | Year | 2017 |
| Journal | Hypertension | Volume | 69 |
| Issue | 1 | Pages | 79-86 |
| PubMed ID | 27895190 | Mgi Jnum | J:280987 |
| Mgi Id | MGI:6376360 | Doi | 10.1161/HYPERTENSIONAHA.116.08278 |
| Citation | Forrester SJ, et al. (2017) Caveolin-1 Deletion Prevents Hypertensive Vascular Remodeling Induced by Angiotensin II. Hypertension 69(1):79-86 |
| abstractText | It has been proposed that membrane microdomains, caveolae, in vascular cells are critical for signal transduction and downstream functions induced by angiotensin II (AngII). We have tested our hypothesis that caveolin-1 (Cav1), a major structural protein of vascular caveolae, plays a critical role in the development of vascular remodeling by AngII via regulation of epidermal growth factor receptor and vascular endothelial adhesion molecule-1. Cav1(-/-) and control Cav(+/+) mice were infused with AngII for 2 weeks to induce vascular remodeling and hypertension. On AngII infusion, histological assessments demonstrated medial hypertrophy and perivascular fibrosis of aorta and coronary and renal arteries in Cav1(+/+) mice compared with sham-operated Cav1(+/+) mice. AngII-infused Cav1(+/+) mice also showed a phenotype of cardiac hypertrophy with increased heart weight to body weight ratio compared with control Cav1(+/+) mice. In contrast, Cav1(-/-) mice infused with AngII showed attenuation of vascular remodeling but not cardiac hypertrophy. Similar levels of AngII-induced hypertension were found in both Cav1(+/+) and Cav1(-/-) mice as assessed by telemetry. In Cav1(+/+) mice, AngII enhanced tyrosine-phosphorylated epidermal growth factor receptor staining in the aorta, which was attenuated in Cav1(-/-) mice infused with AngII. Enhanced Cav1 and vascular endothelial adhesion molecule-1 expression was also observed in aorta from AngII-infused Cav1(+/+) mice but not in Cav1(-/-) aorta. Experiments with vascular cells further provided a potential mechanism for our in vivo findings. These data suggest that Cav1, and presumably caveolae, in vascular smooth muscle and the endothelium plays a critical role in vascular remodeling and inflammation independent of blood pressure or cardiac hypertrophy regulation. |
