Elevated pulmonary arterial pressure and altered expression ofDdah1andArg1in mice lacking cavin-1/PTRF

Abstract

Caveolae are invaginations in the plasma membrane that depend on caveolins and cavins for maturation. Here, we investigated the pulmonary phenotype in mice lacking cavin-1. Bright field and electron-microscopy showed that the cavin-1-deficient mice lacked caveolae in the lung, had an increased lung tissue density, and exhibited hypertrophic remodeling of pulmonary arteries. The right ventricle of the heart moreover had an increased mass and the right ventricular pressure was elevated. A microarray analysis revealed upregulation of Arg1 and downregulation of Ddah1, molecules whose altered expression has previously been associated with pulmonary arterial hypertension. Taken together, this work demonstrates vascular remodeling and increased pulmonary blood pressure in cavin-1 deficient mice and associates this phenotype with altered expression of Arg1 and Ddah1.

Vasopressin-induced mouse urethral contraction is modulated by caveolin-1

“…Given the apparently high cavin-3/cavin-2 expression ratio in smooth muscle tissues, it will be of interest to examine the impact of cavin-3 deletion on smooth muscle function in future work. It may however be difficult to dissect the role of Cav1 from that of cavin-1 and cavin-3 because these proteins affect each other's stability in smooth muscle (Karbalaei et al, 2012;Swärd et al, 2013).…”

Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular smooth muscle cells and exacerbates abdominal aortic aneurysm

“…In addition, Cav-1 in macrophages regulates phagocytosis and intracellular cholesterol metabolism [13,14]. Among cavins, polymerase I and transcript release factor (PTRF)/Cavin-1 deficiency has been demonstrated to cause elevated pulmonary arterial pressure accompanying hypertrophic remodeling of pulmonary arteries, but maintained systemic blood pressure despite arterial dysfunction [15,16]. Thus, some of caveolae-associated proteins are involved in the process of vascular disease.…”

Myocardin Family Members Drive Formation of Caveolae

“…Cavins, for example, are cytosolic proteins forming distinct sub-complexes that cover the cytosolic surface of caveolae [ 3 , 4 ]. Genetic deletion of cavins leads to partial [ 5 – 7 ] or complete [ 8 – 10 ] loss of caveolae as does deletion of caveolins [ 11 , 12 ]. Two other proteins, Pacsin2 and Ehd2, also play roles for the membrane curvature in caveolae [ 13 ] and for their membrane confinement [ 14 ].…”