Reexpression of caveolin-1 in endothelium rescues the vascular, cardiac, and pulmonary defects in global caveolin-1 knockout mice.

Abstract

Caveolin-1 (Cav-1) is the principal structural component of caveolae organelles in smooth muscle cells, adipocytes, fibroblasts, epithelial cells, and endothelial cells (ECs). Cav-1-deficient (Cav-1 knockout [KO]) mice are viable and show increases of nitric oxide (NO) production in vasculature, cardiomyopathy, and pulmonary dysfunction. In this study, we generated EC-specific Cav-1-reconstituted (Cav-1 RC) mice and reexamined vascular, cardiac, and pulmonary phenotypes. Cav-1 KO pulmonary arteries had decreased smooth muscle contractility and increased endothelial NO synthase activation and hypotension; the latter two effects were rescued completely in Cav-1 RC mice. Cav-1 KO mice exhibited myocardial hypertrophy, pulmonary hypertension, and alveolar cell hyperproliferation caused by constitutive activation of p42/44 mitogen-activated protein kinase and Akt. Interestingly, in Cav-1 RC mice, cardiac hypertrophy and pulmonary hypertension were completely rescued, whereas alveolar hyperplasia was partially recovered because of the lack of rescue of Cav-1 in bronchiolar epithelial cells. These results provide clear physiological evidence supporting the important role of cell type-specific Cav-1 expression governing multiple phenotypes in the vasculature, heart, and lung.

• Authors: Takahisa Murata, Michelle I Lin, Yan Huang, Jun Yu, Phillip Michael Bauer, Frank J Giordano, William C Sessa
• Journal: The Journal of experimental medicine (J Exp Med) Vol. 204 Issue 10 Pg. 2373-82 (Oct 01 2007) ISSN: 0022-1007 [Print] United States
• PMID: 17893196 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Caveolin 1
• Collagen
• Nitric Oxide Synthase Type III

Topics

• Animals
• Blood Vessels (metabolism, pathology)
• Body Weight
• Caveolin 1 (deficiency, genetics, metabolism)
• Collagen (biosynthesis)
• Endothelium (metabolism)
• Gene Expression Regulation
• Heart Defects, Congenital (genetics, metabolism, pathology)
• Hypertension, Pulmonary (genetics, metabolism, pathology)
• Lung Diseases (genetics, metabolism, pathology)
• Mice
• Mice, Knockout
• Myocardial Contraction
• Nitric Oxide Synthase Type III (metabolism)
• Phenotype
• Signal Transduction