Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387270147> ?p ?o ?g. }
Showing items 1 to 86 of
86
with 100 items per page.
- W4387270147 abstract "Coronary artery disease caused by atherosclerosis is a leading cause of morbidity and mortality. Vascular calcification, influenced by inflammation, is associated with atherosclerotic disease burden and increased risk of cardiovascular events. The small GTPase Rac1 is an important signal transducer of inflammatory cytokine expression. We sought to define the mechanisms whereby Rac1 and its activating guanine nucleotide exchange factor (GEF), Tiam1, regulate macrophage expression of the potent inflammatory cytokine, IL-1β, and consequent calcific atherosclerotic vascular disease. To define the role of macrophage Rac1 expression on IL-1β expression and atherosclerotic calcification, we developed mouse models on the atherosclerosis-prone background, including inducible myeloid Rac1 -deletion (mR1KO) ( CSF1 mcm Rac1 fl/fl ApoE -/-) , and global Tiam1- deletion ( Tiam1 -/- ApoE -/- ). Both Rac1-deleted and Tiam1-deleted macrophages demonstrated reduced IL-1β expression in an inflammasome-stimulation assay. Macrophage Rac1 -deletion led to decreased nuclear NF-κB activity and reduced NF-κB and GTP-Rac1 binding to the IL-1β promoter by chromatin immunoprecipitation assay (ChIP). Using an inflammatory stimulus, we found that Rac1 and NF-κB form a protein complex by Proximity Ligation Assay, which is disrupted by Rac1- deletion. Gain-of-function mutations for Rac1 rescued IL-1β expression in Rac1-deleted macrophages, and mutations in the hypervariable region of Rac1 confirmed that the nuclear localization of Rac1 is required for the rescue of IL-1β expression. This recent preliminary data demonstrated that the small GTPase, Rac1, acts as a transcriptional co-factor, helping to activate NF-κB, facilitating NF-κB’s translocation to the nucleus, and binding the IL-1β promoter. In a hyperlipidemia model of experimental atherosclerosis, macrophage Rac1- deletion reduced systemic IL-1β levels and decreased plaque calcification. Targeted inhibition of the macrophage Tiam1-Rac1 signaling complex may have potential as a therapeutic strategy to mitigate inflammatory-driven vascular calcification, given that small molecule inhibitors of Tiam1-Rac1 already exist." @default.
- W4387270147 created "2023-10-03" @default.
- W4387270147 creator A5001421296 @default.
- W4387270147 creator A5018421980 @default.
- W4387270147 creator A5030182835 @default.
- W4387270147 creator A5035534538 @default.
- W4387270147 creator A5048863906 @default.
- W4387270147 creator A5056118732 @default.
- W4387270147 creator A5056347700 @default.
- W4387270147 creator A5060961498 @default.
- W4387270147 creator A5065575314 @default.
- W4387270147 creator A5066721459 @default.
- W4387270147 creator A5078872908 @default.
- W4387270147 creator A5083344738 @default.
- W4387270147 creator A5089623165 @default.
- W4387270147 creator A5092989548 @default.
- W4387270147 date "2023-05-01" @default.
- W4387270147 modified "2023-10-03" @default.
- W4387270147 title "Abstract 435: Macrophage Rac1 As A Transcriptional Co-factor For NF-kb-driven IL-1β Expression And Consequent Atherosclerotic Calcification" @default.
- W4387270147 doi "https://doi.org/10.1161/atvb.43.suppl_1.435" @default.
- W4387270147 hasPublicationYear "2023" @default.
- W4387270147 type Work @default.
- W4387270147 citedByCount "0" @default.
- W4387270147 crossrefType "journal-article" @default.
- W4387270147 hasAuthorship W4387270147A5001421296 @default.
- W4387270147 hasAuthorship W4387270147A5018421980 @default.
- W4387270147 hasAuthorship W4387270147A5030182835 @default.
- W4387270147 hasAuthorship W4387270147A5035534538 @default.
- W4387270147 hasAuthorship W4387270147A5048863906 @default.
- W4387270147 hasAuthorship W4387270147A5056118732 @default.
- W4387270147 hasAuthorship W4387270147A5056347700 @default.
- W4387270147 hasAuthorship W4387270147A5060961498 @default.
- W4387270147 hasAuthorship W4387270147A5065575314 @default.
- W4387270147 hasAuthorship W4387270147A5066721459 @default.
- W4387270147 hasAuthorship W4387270147A5078872908 @default.
- W4387270147 hasAuthorship W4387270147A5083344738 @default.
- W4387270147 hasAuthorship W4387270147A5089623165 @default.
- W4387270147 hasAuthorship W4387270147A5092989548 @default.
- W4387270147 hasConcept C101762097 @default.
- W4387270147 hasConcept C104317684 @default.
- W4387270147 hasConcept C126619667 @default.
- W4387270147 hasConcept C134320426 @default.
- W4387270147 hasConcept C150194340 @default.
- W4387270147 hasConcept C153911025 @default.
- W4387270147 hasConcept C203014093 @default.
- W4387270147 hasConcept C2776914184 @default.
- W4387270147 hasConcept C2777209026 @default.
- W4387270147 hasConcept C2779717556 @default.
- W4387270147 hasConcept C502942594 @default.
- W4387270147 hasConcept C54355233 @default.
- W4387270147 hasConcept C62478195 @default.
- W4387270147 hasConcept C86803240 @default.
- W4387270147 hasConcept C95444343 @default.
- W4387270147 hasConceptScore W4387270147C101762097 @default.
- W4387270147 hasConceptScore W4387270147C104317684 @default.
- W4387270147 hasConceptScore W4387270147C126619667 @default.
- W4387270147 hasConceptScore W4387270147C134320426 @default.
- W4387270147 hasConceptScore W4387270147C150194340 @default.
- W4387270147 hasConceptScore W4387270147C153911025 @default.
- W4387270147 hasConceptScore W4387270147C203014093 @default.
- W4387270147 hasConceptScore W4387270147C2776914184 @default.
- W4387270147 hasConceptScore W4387270147C2777209026 @default.
- W4387270147 hasConceptScore W4387270147C2779717556 @default.
- W4387270147 hasConceptScore W4387270147C502942594 @default.
- W4387270147 hasConceptScore W4387270147C54355233 @default.
- W4387270147 hasConceptScore W4387270147C62478195 @default.
- W4387270147 hasConceptScore W4387270147C86803240 @default.
- W4387270147 hasConceptScore W4387270147C95444343 @default.
- W4387270147 hasIssue "Suppl_1" @default.
- W4387270147 hasLocation W43872701471 @default.
- W4387270147 hasOpenAccess W4387270147 @default.
- W4387270147 hasPrimaryLocation W43872701471 @default.
- W4387270147 hasRelatedWork W1905949153 @default.
- W4387270147 hasRelatedWork W1964171635 @default.
- W4387270147 hasRelatedWork W1986074141 @default.
- W4387270147 hasRelatedWork W1993756444 @default.
- W4387270147 hasRelatedWork W2002122463 @default.
- W4387270147 hasRelatedWork W2051751591 @default.
- W4387270147 hasRelatedWork W2140841583 @default.
- W4387270147 hasRelatedWork W2162049443 @default.
- W4387270147 hasRelatedWork W2554221370 @default.
- W4387270147 hasRelatedWork W3201655071 @default.
- W4387270147 hasVolume "43" @default.
- W4387270147 isParatext "false" @default.
- W4387270147 isRetracted "false" @default.
- W4387270147 workType "article" @default.