Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice

Caveolae are plasma membrane invaginations that may play an important role in numerous cellular processes including transport, signaling, and tumor su ppression. By targeted disruption of caveolin-1, the main protein component of caveolae, we generated mice that lacked caveolae. The absence of this o rganelle impaired nitric oxide and calcium signaling in the cardiovascular system, causing aberrations in endothelium-dependent relaxation, contractil ity, and maintenance of myogenic tone. In addition, the lungs of knockout a nimals displayed thickening of alveolar septa caused by uncontrolled endoth elial cell proliferation and fibrosis, resulting in severe physical limitat ions in caveolin-1-disrupted mice. Thus, caveolin-1 and caveolae play a fun damental role in organizing multiple signaling pathways in the cell.