Hypertension In Knockout Mice Research Articles

Caveolin-1: a critical regulator of pulmonary vascular architecture and nitric oxide bioavailability in pulmonary hypertension

caveolae are 50- to 100-nm ω-shaped invaginations of the cell surface plasma membrane enriched in glycosphingolipids and cholesterol that occur in a variety of cell types including epithelial and endothelial cells, fibroblasts, smooth muscle cells, and adipocytes ([1][1]). These structures

S7-03 Defects in caveolin-1 causes dilated cardiomyopathyand pulmonary hypertension in knockout mice

S7-03 Defects in caveolin-1 causes dilated cardiomyopathyand pulmonary hypertension in knockout mice

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

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.