Endothelial-specific Expression of Caveolin-1 Impairs Microvascular Permeability and Angiogenesis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2004 Dec 24

PMID 15615855

Citations 75

Authors

Philip M Bauer

Jun Yu

Yan Chen

Reed Hickey

Pascal N Bernatchez

Robin Looft-Wilson

Yan Huang

Frank Giordano

Radu V Stan

William C Sessa

Affiliations

Soon will be listed here.

Abstract

The functions of caveolae and/or caveolins in intact animals are beginning to be explored. Here, by using endothelial cell-specific transgenesis of the caveolin-1 (Cav-1) gene in mice, we show the critical role of Cav-1 in several postnatal vascular paradigms. First, increasing levels of Cav-1 do not increase caveolae number in the endothelium in vivo. Second, despite a lack of quantitative changes in organelle number, endothelial-specific expression of Cav-1 impairs endothelial nitric oxide synthase activation, endothelial barrier function, and angiogenic responses to exogenous VEGF and tissue ischemia. In addition, VEGF-mediated phosphorylation of Akt and its substrate, endothelial nitric oxide synthase, were significantly reduced in VEGF-treated Cav-1 transgenic mice, compared with WT littermates. The inhibitory effect of Cav-1 expression on the Akt-endothelial nitric oxide synthase pathway was specific because VEGF-stimulated phosphorylation of mitogen-activated protein kinase (ERK1/2) was elevated in the Cav-1 transgenics, compared with littermates. These data strongly support the idea that, in vivo, Cav-1 may modulate signaling pathways independent of its essential role in caveolae biogenesis.

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