Cavin-1: caveolae-dependent signalling and cardiovascular disease

2014 ◽  
Vol 42 (2) ◽  
pp. 284-288 ◽  
Author(s):  
Jamie J.L. Williams ◽  
Timothy M. Palmer
Keyword(s):  
Cardiovascular Disease ◽  
Signal Transduction ◽  
Vascular Endothelial Cells ◽  
Integral Membrane Protein ◽  
Vascular Endothelial ◽  
Caveolin 1 ◽  
Disease States ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

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 compartmentalized for efficient signal transduction. Many of these receptors, including cytokine signal transducer gp130 (glycoprotein 130), 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 stabilizes caveolin-1, the main structural/integral membrane protein of caveolae. Caveolin-1 is an essential regulator of eNOS (endothelial nitric oxide synthase) and its disruption leads to endothelial dysfunction which initiates a range of cardiovascular and pulmonary disorders. Although 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. The present review introduces caveolae, their structural components, the caveolins and cavins, their regulation by cAMP, and their potential role in cardiovascular disease.

scholarly journals Shear stress augments mitochondrial ATP generation that triggers ATP release and Ca2+ signaling in vascular endothelial cells

2018 ◽  
Vol 315 (5) ◽  
pp. H1477-H1485 ◽  
Author(s):  
Kimiko Yamamoto ◽  
Hiromi Imamura ◽  
Joji Ando
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Vascular Endothelial Cells ◽  
Critical Role ◽  
Atp Release ◽  
Vascular Endothelial ◽  
The Novel ◽  
Caveolin 1 ◽  
Atp Generation

Vascular endothelial cells (ECs) sense and transduce hemodynamic shear stress into intracellular biochemical signals, and Ca2+ signaling plays a critical role in this mechanotransduction, i.e., ECs release ATP in the caveolae in response to shear stress and, in turn, the released ATP activates P2 purinoceptors, which results in an influx into the cells of extracellular Ca2+. However, the mechanism by which the shear stress evokes ATP release remains unclear. Here, we demonstrated that cellular mitochondria play a critical role in this process. Cultured human pulmonary artery ECs were exposed to controlled levels of shear stress in a flow-loading device, and changes in the mitochondrial ATP levels were examined by real-time imaging using a fluorescence resonance energy transfer-based ATP biosensor. Immediately upon exposure of the cells to flow, mitochondrial ATP levels increased, which was both reversible and dependent on the intensity of shear stress. Inhibitors of the mitochondrial electron transport chain and ATP synthase as well as knockdown of caveolin-1, a major structural protein of the caveolae, abolished the shear stress-induced mitochondrial ATP generation, resulting in the loss of ATP release and influx of Ca2+ into the cells. These results suggest the novel role of mitochondria in transducing shear stress into ATP generation: ATP generation leads to ATP release in the caveolae, triggering purinergic Ca2+ signaling. Thus, exposure of ECs to shear stress seems to activate mitochondrial ATP generation through caveola- or caveolin-1-mediated mechanisms. NEW & NOTEWORTHY The mechanism of how vascular endothelial cells sense shear stress generated by blood flow and transduce it into functional responses remains unclear. Real-time imaging of mitochondrial ATP demonstrated the novel role of endothelial mitochondria as mechanosignaling organelles that are able to transduce shear stress into ATP generation, triggering ATP release and purinoceptor-mediated Ca2+ signaling within the cells.

Sign in / Sign up

Export Citation Format

Share Document