Proceedings of the National Academy of Sciences of the United States of America
Geisel School of Medicine
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.
Bauer PM, Yu J, Chen Y, Hickey R, Bernatchez PN, Looft-Wilson R, Huang Y, Giordano F, Stan RV, Sessa WC. Endothelial-specific expression of caveolin-1 impairs microvascular permeability and angiogenesis. Proc Natl Acad Sci U S A. 2005 Jan 4;102(1):204-9. doi: 10.1073/pnas.0406092102. Epub 2004 Dec 22. PMID: 15615855; PMCID: PMC544041.
Dartmouth Digital Commons Citation
Bauer, Philip M.; Yu, Jun; Chen, Yan; Hickey, Reed; Bernatchez, Pascal N.; Looft-Wilson, Robin; Huang, Yan; Giordano, Frank; Stan, Radu V.; and Sessa, William C., "Endothelial-Specific Expression of Caveolin-1 Impairs Microvascular Permeability and Angiogenesis" (2005). Dartmouth Scholarship. 1720.