Cavin-1: caveolae-dependent signalling and cardiovascular disease

Williams, Jamie J.L.; Palmer, Timothy M.

doi:10.1042/bst20130270

Cited by 28 publications

(23 citation statements)

References 47 publications

(72 reference statements)

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“…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.…”

Section: Discussionsupporting

confidence: 60%

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

et al. 2015

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We hypothesized that lack of the high-energy phosphates during liver storage may potentially cause persistent injury to the vascular endothelium. Biopsies were obtained from livers obtained from beating heart human donors, stored either in the standard storage solution, that is, University of Wisconsin solution (UWS) or Celsior, and examined for various markers related to progressive endothelial injury. The expression of P2Y1 receptor, the major signal transduction machinery for adenosine triphosphate/adenosine diphosphate, decreased in hepatic vascular endothelial cells over time. Despite unaltered endothelial nitric oxide synthase (eNOS) levels, serine1177-phosphorylated eNOS, the active form of eNOS, progressively decreased with time. The production of nitric oxide enzyme decreased with time when liver tissues were examined in vitro. This also coincided with decreased interaction of eNOS with actin nucleating proteins like myristoylated alanine-rich C kinase substrate and Rac1, which plays a role in modulating the cytoskeleton and helps position eNOS in a favorable cytosolic position for active enzymatic activity. Conversely, the interaction of eNOS with caveolin1 was significantly increased 6 H after ex vivo storage. Finally, we demonstrated by targeted contrast-enhanced ultrasound that membrane-bound vascular cell adhesion molecule-1 in the hepatic vascular endothelial cell increased after 6 H of ex vivo storage. Overall, the results of this study provide evidence of a progressive hepatic vascular endothelial injury during the ex vivo storage. This may be a causative factor for ischemic cholangiopathy and delayed graft function post liver transplantation. V C 2015 IUBMB Life, 68(1): [51][52][53][54][55][56][57] 2015

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Section: Discussionsupporting

confidence: 60%

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

et al. 2015

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“…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 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2014

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Endothelial cells are important elements in the vascular response to danger-associated molecules signaling through toll-like receptors (TLRs). Flotillin-1 and -2 are markers of membrane rafts but their true endothelial function is unknown. We hypothesized that flotillins are required for TLR signaling in human umbilical vein endothelial cells (HUVECs). Knockdown of flotillin-1 by shRNA decreased the TLR3-mediated poly-I:C-induced but not the TLR4-mediated LPS-induced inflammatory activation of HUVEC. As TLR3 but not TLR4 signals through the endosomal compartment, flotillin-1 might be involved in the transport of poly-I:C to its receptor. Consistently, uptake of poly-I:C was attenuated by flotillin-1 knockdown and probably involved the scavenger receptor SCARA4 as revealed by knockdown of this receptor. To determine the underlying mechanism, SILAC proteomics was performed. Down-regulation of flotillin-1 led to a reduction of the structural caveolae proteins caveolin-1, cavin-1 and -2, suggesting a role of flotillin-1 in caveolae formation. Flotillin-1 and caveolin-1 colocalized within the cell, and knockdown of flotillin-1 decreased caveolin-1 expression in an endoplasmic reticulum stress-dependent manner. Importantly, downregulation of caveolin-1 also attenuated TLR3-induced signaling. To demonstrate the importance of this finding, cell adhesion was studied. Flotillin-1 shRNA attenuated the poly-I:C-mediated induction of the adhesion molecules VCAM-1 and ICAM-1. As a consequence, the poly-I:C-induced adhesion of peripheral blood mononuclear cells onto HUVECs was significantly attenuated by flotillin-1 shRNA. Collectively, these data suggest that interaction between flotillin-1 and caveolin-1 may facilitate the transport of TLR3-ligands to its intracellular receptor and enables inflammatory TLR3 signaling.Electronic supplementary materialThe online version of this article (doi:10.1007/s00395-014-0439-4) contains supplementary material, which is available to authorized users.

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“…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 ].…”

Section: Influence Of N-3 Pufa On Endothelial Functionmentioning

confidence: 99%

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

Zanetti

Grillo

Losurdo

et al. 2015

BioMed Research International

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Omega-3 polyunsaturated fatty acids (n-3 PUFA) consumption is associated with reduced cardiovascular disease risk. Increasing evidence demonstrating a beneficial effect of n-3 PUFA on arterial wall properties is progressively emerging. We reviewed the recent available evidence for the cardiovascular effects of n-3 PUFA focusing on structural and functional properties of the vascular wall. In experimental studies and clinical trials n-3 PUFA have shown the ability to improve arterial hemodynamics by reducing arterial stiffness, thus explaining some of its cardioprotective properties. Recent studies suggest beneficial effects of n-3 PUFA on endothelial activation, which are likely to improve vascular function. Several molecular, cellular, and physiological pathways influenced by n-3 PUFA can affect arterial wall properties and therefore interfere with the atherosclerotic process. Although the relative weight of different physiological and molecular mechanisms and the dose-response on arterial wall properties have yet to be determined, n-3 PUFA have the potential to beneficially impact arterial wall remodeling and cardiovascular outcomes by targeting arterial wall stiffening and endothelial dysfunction.

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Cavin-1: caveolae-dependent signalling and cardiovascular disease

Cited by 28 publications

References 47 publications

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

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

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

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

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