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

You Yang Zhao, Yang Liu, Radu Virgil Stan, Lian Fan, Yusu Gu, Nancy Dalton, Po Hsien Chu, Kirk Peterson, John Ross, Kenneth R. Chien*

*Corresponding author for this work

Research output: Contribution to journalArticle

348 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)11375-11380
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume99
Issue number17
DOIs
StatePublished - Aug 20 2002

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