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

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- specifi c 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 - specifi c Cav- 1 expression governing multiple phenotypes in the vasculature, heart, and lung.