TNFα-Induced Inflammation Is Mediated by WNT/β-Catenin Signalling in Endothelial Cells: Implications for Atherosclerosis: BSCR Autumn Meeting Abstracts

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Abstract

Atherosclerosis leads to coronary artery disease and affects over 2.3 millionindividuals in the UK and is the main cause of death worldwide.Atherosclerosis is a chronic and inflammatory condition involving depositionof low-density lipoprotein and formation of a plaque within thearterial wall which can rupture and lead to thrombosis and blockage ofthe artery. Atherosclerosis involves endothelial dysfunction and associatedinflammation. Tumour necrosis factor-α (TNF-α) is believed to play amajor role in the initiation of endothelial dysfunction and inflammation.In this study, we determined whether TNF-α-induced inflammation wasregulated by Wnt/β-catenin signalling. To examine this, HUVECs weretreated with 10 ng/ml TNF-α for 24 h. Using qPCR, inflammatory geneexpression was quantified. TNF-α significantly increasedMCP-1 mRNAby 41 ± 9-fold (p < 0.05, n = 9). ELISA confirmed that MCP-1 proteinexpression was significantly increased to 24,319 ± 1207 pg/ml from550 ± 550 pg/ml (p < 0.05, n = 4). Interestingly TNF-α significantly reduced Axin-2 mRNA expression (a suppressor of Wnt/β-catenin signalling)by over 40% (p < 0.05, n = 9), suggesting that Wnt/β-catenin signallingwas enhanced as a result of TNF-α. To test the involvement ofWnt/β-catenin signalling in TNF-α response, it was inhibited with iCRT14 (β-catenin inhibitor) and ETC-1922159 (Wnt inhibitor) andagonised with Wnt3a and Wnt5a. Inhibition of Wnt/β-catenin signallingsignificantly attenuated the induction ofMCP-1 protein by TNF-α, whilerecombinant Wnt3a and Wnt5a increased MCP-1 protein expression to1734 ± 883 and 936 ± 540 pg/ml (p < 0.05, n = 4). In conclusion, TNF-α-induced MCP-1 expression is mediated at least in part by Wnt/β-cateninsignalling and this may contribute to the inflammation of endothelial cellsin atherosclerosis.
Original languageEnglish
Pages270-271
Number of pages2
DOIs
Publication statusPublished - 16 Apr 2019
EventBRITISH SOCIETY FOR CARDIOVASCULAR RESEARCH AUTUMN MEETING - Bristol, United Kingdom
Duration: 1 Sep 2008 → …

Conference

ConferenceBRITISH SOCIETY FOR CARDIOVASCULAR RESEARCH AUTUMN MEETING
CountryUnited Kingdom
CityBristol
Period1/09/08 → …

Keywords

  • Atherosclerosis
  • Saphenous Vein Graft Failure
  • Endothelial Cells
  • Bypass Graft

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