title: Caveolin-1 Deletion Prevents Hypertensive Vascular Remodeling Induced by Angiotensin II.
abstract: 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.
authors.affiliation: From the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.J.F., K.J.E., T.K., T.O., M.J.B., K.J.P., S.E., V.R.); and Department of Medicine, University of Virginia, Charlottesville (Z.Y.).
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Forrester
authors.affiliation: From the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.J.F., K.J.E., T.K., T.O., M.J.B., K.J.P., S.E., V.R.); and Department of Medicine, University of Virginia, Charlottesville (Z.Y.).
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Elliott
authors.affiliation: From the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.J.F., K.J.E., T.K., T.O., M.J.B., K.J.P., S.E., V.R.); and Department of Medicine, University of Virginia, Charlottesville (Z.Y.).
authors.forename: Tatsuo
authors.initials: T
authors.lastname: Kawai
authors.affiliation: From the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.J.F., K.J.E., T.K., T.O., M.J.B., K.J.P., S.E., V.R.); and Department of Medicine, University of Virginia, Charlottesville (Z.Y.).
authors.forename: Takashi
authors.initials: T
authors.lastname: Obama
authors.affiliation: From the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.J.F., K.J.E., T.K., T.O., M.J.B., K.J.P., S.E., V.R.); and Department of Medicine, University of Virginia, Charlottesville (Z.Y.).
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Boyer
authors.affiliation: From the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.J.F., K.J.E., T.K., T.O., M.J.B., K.J.P., S.E., V.R.); and Department of Medicine, University of Virginia, Charlottesville (Z.Y.).
authors.forename: Kyle J
authors.initials: KJ
authors.lastname: Preston
authors.affiliation: From the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.J.F., K.J.E., T.K., T.O., M.J.B., K.J.P., S.E., V.R.); and Department of Medicine, University of Virginia, Charlottesville (Z.Y.).
authors.forename: Zhen
authors.initials: Z
authors.lastname: Yan
authors.affiliation: From the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.J.F., K.J.E., T.K., T.O., M.J.B., K.J.P., S.E., V.R.); and Department of Medicine, University of Virginia, Charlottesville (Z.Y.).
authors.forename: Satoru
authors.initials: S
authors.lastname: Eguchi
authors.affiliation: From the Cardiovascular Research Center, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (S.J.F., K.J.E., T.K., T.O., M.J.B., K.J.P., S.E., V.R.); and Department of Medicine, University of Virginia, Charlottesville (Z.Y.) rizzov@temple.edu seguchi@temple.edu.
authors.forename: Victor
authors.initials: V
authors.lastname: Rizzo
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D051242:Caveolin 1 / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D017353:Gene Deletion; D006973:Hypertension / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D066253:Vascular Remodeling / Q000187:drug effects / Q000235:genetics*
chemical_list: D051242:Caveolin 1; D000804:Angiotensin II
keywords: angiotensin II; blood pressure; endothelial cells; hypertension; signal transduction