Loss of Caveolae, Vascular Dysfunction, and Pulmonary Defects in Caveolin-1 Gene-Disrupted Mice

TLDR

Caveolae are plasma membrane invaginations involved in transport, signaling, and tumor suppression. Targeted disruption of caveolin‑1, the main caveolae protein, produced mice lacking caveolae. Loss of caveolae in these mice disrupted nitric‑oxide and calcium signaling, causing endothelial dysfunction and altered vascular tone, and in the lungs induced alveolar septal thickening from endothelial proliferation and fibrosis that severely limited physical function, underscoring caveolin‑1’s role in coordinating multiple signaling pathways.

Abstract

Caveolae are plasma membrane invaginations that may play an important role in numerous cellular processes including transport, signaling, and tumor suppression. By targeted disruption of caveolin-1, the main protein component of caveolae, we generated mice that lacked caveolae. The absence of this organelle impaired nitric oxide and calcium signaling in the cardiovascular system, causing aberrations in endothelium-dependent relaxation, contractility, and maintenance of myogenic tone. In addition, the lungs of knockout animals displayed thickening of alveolar septa caused by uncontrolled endothelial cell proliferation and fibrosis, resulting in severe physical limitations in caveolin-1-disrupted mice. Thus, caveolin-1 and caveolae play a fundamental role in organizing multiple signaling pathways in the cell.