Cavin-1: caveolae-dependent signalling and cardiovascular disease

Abstract

Caveolae are curved lipid raft regions rich in cholesterol and sphingolipids found abundantly in vascular endothelial cells, adipocytes, smooth muscle cells, and fibroblasts. They are multifunctional organelles with roles in clathrin-independent endocytosis, cholesterol transport, mechanosensing, and signal transduction. Caveolae provide an environment where multiple receptor signalling components are sequestered, clustered, and compartmentalised for efficient signal transduction. Many of these receptors, including cytokine signal transducer gp130, are mediators of chronic inflammation during atherogenesis. Subsequently, disruption of these organelles is associated with a broad-range of disease states including cardiovascular disease and cancer. Cavin-1 is an essential peripheral component of caveolae that stabilises caveolin-1, the main structural/integral membrane protein of caveolae. Caveolin-1 is an essential regulator of endothelial nitric oxide synthase (eNOS) and its disruption leads to endothelial dysfunction which initiates a range of cardiovascular and pulmonary disorders. While dysfunctional cytokine signalling is also a hallmark of cardiovascular disease, knowledge of caveolae-dependent cytokine signalling is lacking as is the role of cavin-1 independent of caveolae. This review will introduce caveolae, its structural components, the caveolins and cavins, their regulation by cAMP, and their potential role in cardiovascular disease.