FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2804304881> ?p ?o ?g. }

• W2804304881 endingPage "10589" @default.
• W2804304881 startingPage "10574" @default.
• W2804304881 abstract "Although signaling of thrombin via its receptor protease-activated receptor 1 (Par1) is known to occur in atherothrombosis, its link to the actual pathogenesis of this condition is less clear. To better understand the role of thrombin–Par1 signaling in atherosclerosis, here we have studied their effects on cellular cholesterol efflux in mice. We found that by activating Par1 and cullin 3–mediated ubiquitination and degradation of ABC subfamily A member 1 (ABCA1), thrombin inhibits cholesterol efflux in both murine macrophages and smooth muscle cells. Moreover, disruption of the Par1 gene rescued ABCA1 from Western diet–induced ubiquitination and degradation and restored cholesterol efflux in apolipoprotein E–deficient (ApoE−/−) mice. Similarly, the Par1 deletion diminished diet-induced atherosclerotic lesions in the ApoE−/− mice. These observations for the first time indicate a role for thrombin–Par1 signaling in the pathogenesis of diet-induced atherosclerosis. We identify cullin 3 as a cullin-RING ubiquitin E3 ligase that mediates ABCA1 ubiquitination and degradation and thereby inhibits cholesterol efflux. Furthermore, compared with peripheral blood mononuclear cells (PBMCs) from ApoE−/− mice, the PBMCs from ApoE−/−:Par1−/− mice exhibited decreased trafficking to inflamed arteries of Western diet–fed ApoE−/− mice. This finding suggested that besides inhibiting cholesterol efflux, thrombin–Par1 signaling also plays a role in the recruitment of leukocytes during diet-induced atherogenesis. Based on these findings, we conclude that thrombin–Par1 signaling appears to contribute to the pathogenesis of atherosclerosis by impairing cholesterol efflux from cells and by recruiting leukocytes to arteries. Although signaling of thrombin via its receptor protease-activated receptor 1 (Par1) is known to occur in atherothrombosis, its link to the actual pathogenesis of this condition is less clear. To better understand the role of thrombin–Par1 signaling in atherosclerosis, here we have studied their effects on cellular cholesterol efflux in mice. We found that by activating Par1 and cullin 3–mediated ubiquitination and degradation of ABC subfamily A member 1 (ABCA1), thrombin inhibits cholesterol efflux in both murine macrophages and smooth muscle cells. Moreover, disruption of the Par1 gene rescued ABCA1 from Western diet–induced ubiquitination and degradation and restored cholesterol efflux in apolipoprotein E–deficient (ApoE−/−) mice. Similarly, the Par1 deletion diminished diet-induced atherosclerotic lesions in the ApoE−/− mice. These observations for the first time indicate a role for thrombin–Par1 signaling in the pathogenesis of diet-induced atherosclerosis. We identify cullin 3 as a cullin-RING ubiquitin E3 ligase that mediates ABCA1 ubiquitination and degradation and thereby inhibits cholesterol efflux. Furthermore, compared with peripheral blood mononuclear cells (PBMCs) from ApoE−/− mice, the PBMCs from ApoE−/−:Par1−/− mice exhibited decreased trafficking to inflamed arteries of Western diet–fed ApoE−/− mice. This finding suggested that besides inhibiting cholesterol efflux, thrombin–Par1 signaling also plays a role in the recruitment of leukocytes during diet-induced atherogenesis. Based on these findings, we conclude that thrombin–Par1 signaling appears to contribute to the pathogenesis of atherosclerosis by impairing cholesterol efflux from cells and by recruiting leukocytes to arteries." @default.
• W2804304881 created "2018-06-01" @default.
• W2804304881 creator A5016376603 @default.
• W2804304881 creator A5026657110 @default.
• W2804304881 creator A5069760561 @default.
• W2804304881 creator A5091775540 @default.
• W2804304881 date "2018-07-01" @default.
• W2804304881 modified "2023-10-06" @default.
• W2804304881 title "Protease-activated receptor 1 inhibits cholesterol efflux and promotes atherogenesis via cullin 3–mediated degradation of the ABCA1 transporter" @default.
• W2804304881 cites W1495670272 @default.
• W2804304881 cites W1525061057 @default.
• W2804304881 cites W1574813722 @default.
• W2804304881 cites W1811402656 @default.
• W2804304881 cites W1972483153 @default.
• W2804304881 cites W1974834921 @default.
• W2804304881 cites W1981285115 @default.
• W2804304881 cites W1992944529 @default.
• W2804304881 cites W2000448320 @default.
• W2804304881 cites W2002231317 @default.
• W2804304881 cites W2004680931 @default.
• W2804304881 cites W2005382591 @default.
• W2804304881 cites W2023820547 @default.
• W2804304881 cites W2025596099 @default.
• W2804304881 cites W2029794495 @default.
• W2804304881 cites W2033883349 @default.
• W2804304881 cites W2034995931 @default.
• W2804304881 cites W2046698436 @default.
• W2804304881 cites W2048890665 @default.
• W2804304881 cites W2052741717 @default.
• W2804304881 cites W2053350354 @default.
• W2804304881 cites W2054738316 @default.
• W2804304881 cites W2058252463 @default.
• W2804304881 cites W2060597789 @default.
• W2804304881 cites W2062403586 @default.
• W2804304881 cites W2064227749 @default.
• W2804304881 cites W2068520355 @default.
• W2804304881 cites W2068886931 @default.
• W2804304881 cites W2073434079 @default.
• W2804304881 cites W2081984884 @default.
• W2804304881 cites W2083215308 @default.
• W2804304881 cites W2093236829 @default.
• W2804304881 cites W2093327629 @default.
• W2804304881 cites W2097389418 @default.
• W2804304881 cites W2105179941 @default.
• W2804304881 cites W2110997510 @default.
• W2804304881 cites W2117847127 @default.
• W2804304881 cites W2128455103 @default.
• W2804304881 cites W2140566999 @default.
• W2804304881 cites W2144854996 @default.
• W2804304881 cites W2145388691 @default.
• W2804304881 cites W2151668213 @default.
• W2804304881 cites W2154843786 @default.
• W2804304881 cites W2155478471 @default.
• W2804304881 cites W2156046019 @default.
• W2804304881 cites W2157280773 @default.
• W2804304881 cites W2161543098 @default.
• W2804304881 cites W2163946154 @default.
• W2804304881 cites W2164634166 @default.
• W2804304881 cites W2286296475 @default.
• W2804304881 cites W2333022264 @default.
• W2804304881 cites W2342173782 @default.
• W2804304881 cites W2345592446 @default.
• W2804304881 cites W2403798563 @default.
• W2804304881 cites W2586704547 @default.
• W2804304881 doi "https://doi.org/10.1074/jbc.ra118.003491" @default.
• W2804304881 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6036195" @default.
• W2804304881 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29777060" @default.
• W2804304881 hasPublicationYear "2018" @default.
• W2804304881 type Work @default.
• W2804304881 sameAs 2804304881 @default.
• W2804304881 citedByCount "25" @default.
• W2804304881 countsByYear W28043048812019 @default.
• W2804304881 countsByYear W28043048812020 @default.
• W2804304881 countsByYear W28043048812021 @default.
• W2804304881 countsByYear W28043048812022 @default.
• W2804304881 countsByYear W28043048812023 @default.
• W2804304881 crossrefType "journal-article" @default.
• W2804304881 hasAuthorship W2804304881A5016376603 @default.
• W2804304881 hasAuthorship W2804304881A5026657110 @default.
• W2804304881 hasAuthorship W2804304881A5069760561 @default.
• W2804304881 hasAuthorship W2804304881A5091775540 @default.
• W2804304881 hasBestOaLocation W28043048811 @default.
• W2804304881 hasConcept C104317684 @default.
• W2804304881 hasConcept C126322002 @default.
• W2804304881 hasConcept C134018914 @default.
• W2804304881 hasConcept C134459356 @default.
• W2804304881 hasConcept C149011108 @default.
• W2804304881 hasConcept C170493617 @default.
• W2804304881 hasConcept C200082930 @default.
• W2804304881 hasConcept C203014093 @default.
• W2804304881 hasConcept C25602115 @default.
• W2804304881 hasConcept C2776330080 @default.
• W2804304881 hasConcept C2777292125 @default.
• W2804304881 hasConcept C2777704780 @default.
• W2804304881 hasConcept C2778163477 @default.
• W2804304881 hasConcept C2778567606 @default.
• W2804304881 hasConcept C2779134260 @default.
• W2804304881 hasConcept C2780072125 @default.

• next