GSE126690 Macrophage ATP citrate lyase deficiency stabilizes atherosclerotic plaques

Contributors : Jeroen Baardman ; Sanne Verberk ; Saskia van der Velden ; Marion Gijbels ; Cindy van Roomen ; Guillermo Griffith ; Koen Prange ; Soufyan Lakbir ; Douwe Molenaar ; Elisa Meinster ; Annette Neele ; Esther Lutgens ; Kathryn Wellen ; Menno de Winther ; Jan Van den BosscheSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusAtherosclerosis is a lipid-driven chronic inflammatory disorder of the arteries in which macrophages are the most prevalent immune cells and define disease development1,2. While macrophages can worsen disease progression by propagating inflammation, they can also stabilize atherosclerotic plaques by promoting the formation of a fibrous cap and by clearing apoptotic cells to prevent necrotic core formation. The last decade, modulation of intracellular metabolic pathways has emerged as a new tool to reshape deranged macrophage functions and is considered as a new therapeutic opportunity3-6. ATP citrate lyase (Acly) catalyzes the conversion of mitochondria-derived citrate into the high-energy acetyl-CoA, but the tools to study this key metabolic hub in macrophages in vivo remained absent. Here, we show Acly to be activated in inflammatory macrophages and in human atherosclerotic plaques and define a formerly unknown role of it in regulating both plaque and macrophage phenotype. Using a novel conditional genetic knockout mouse model, we found that myeloid Acly deficiency induces a stable plaque phenoty...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research