Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice

• DOI: 10.1073/pnas.172360799
• Publication Date: 2002-09-30T16:42:53Z
• Authors: You-Yang Zhao; Yang Liu; Radu-Virgil Stan; Lian Fan; Yusu Gu; Nancy Dalton; Po-Hsien Chu; Kirk Peterson; John Ross; Kenneth R. Chien
• Keywords: Contractility; Dilated Cardiomyopathy; Caveolin 3; Right ventricular hypertrophy

Caveolins are important components of caveolae, which have been implicated in vesicular trafficking and signal transduction. To investigate the vivo significance mammals, we generated mice deficient caveolin-1 (cav-1) gene shown that, absence Cav-1, no caveolae structures were observed several nonmuscle cell types. Although cav-1(-/-) viable, histological examination echocardiography identified a spectrum characteristics dilated cardiomyopathy left ventricular chamber cav-1-deficient hearts, including an enlarged diameter, thin posterior wall, decreased contractility. These animals also marked right hypertrophy, suggesting chronic increase pulmonary artery pressure. Direct measurement pressure analysis revealed that exhibit hypertension, may contribute to ventricle hypertrophy. In addition, loss Cav-1 leads dramatic systemic NO levels. Our studies provided evidence cav-1 is essential for control levels normal cardiopulmonary function.