Cavin-1: caveolae-dependent signalling and cardiovascular disease

Abstract

Supported by a project grant from the Chief Scientist Office [ETM/226] to TMP and a doctoral training studentship from the BBSRC Doctoral Training Programme in Biochemistry and Molecular at the University of Glasgow [BB/F016735/1] to JJLW.Keywords: Cavin-1, caveolae, inflammation, signal transduction, cyclic AMP Abbreviations: MCD: methyl-β-cyclodextrin, STAT: signal transducers and activators of transcription, SOCS: suppressor of cytokine signalling. 2 AbstractCaveolae 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.

Evaluation of hepatic vascular endothelial injury during liver storage by molecular detection and targeted contrast‐enhanced ultrasound imaging

“…Interestingly, the interaction of eNOS with caveolin1 was significantly increased 6 H after ex vivo storage. It has been earlier demonstrated that after nitric oxide synthesis, eNOS gets trapped into caveolae by the caveolin1 protein and this is a major mechanism that participates in termination of activity of eNOS . Overall, the results of this study provide evidence of a progressive endothelial injury of the liver vasculature during ex vivo storage.…”

Flotillin-1 facilitates toll-like receptor 3 signaling in human endothelial cells

“…In endothelial cells, caveolin-1 has complex roles in signaling due to its multiple functions. Translocation of enzymes like endothelial NO synthase into caveolae reduced their activity [ 34 ], whereas translocation of receptors and kinases into caveolae can lead to the formation of signaling hot spots [ 42 ]. Finally, caveolae-mediated uptake of receptors results in termination of signaling or facilitates intracellular signaling [ 3 ].…”

Omega-3 Polyunsaturated Fatty Acids: Structural and Functional Effects on the Vascular Wall

“…The importance of endothelial cell membrane composition has been documented by several studies ( Table 2 ). The reason lies in the fact that endothelial cell membrane houses caveolae and lipid rafts where several receptors and signaling molecules crucial for cell function are concentrated [ 74 ]. Caveolae-associated receptor-mediated cellular signal transduction includes important pathways such as the nitric-oxide cGMP pathway, the NADPH oxidase and TNF- α –NF κ B induced cyclooxygenase-2 (COX-2) and prostaglandin E 2 (PGE 2 ) activation pathway [ 75 , 76 ].…”