title: Macrophage PPAR gamma Co-activator-1 alpha participates in repressing foam cell formation and atherosclerosis in response to conjugated linoleic acid.
abstract: Conjugated linoleic acid (CLA) has the unique property of inducing regression of pre-established murine atherosclerosis. Understanding the mechanism(s) involved may help identify endogenous pathways that reverse human atherosclerosis. Here, we provide evidence that CLA inhibits foam cell formation via regulation of the nuclear receptor coactivator, peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α, and that macrophage PGC-1α plays a role in atheroprotection in vivo. PGC-1α was identified as a hub gene within a cluster in the aorta of the apoE(-/-) mouse in the CLA-induced regression model. PGC-1α was localized to macrophage/foam cells in the murine aorta where its expression was increased during CLA-induced regression. PGC-1α expression was also detected in macrophages in human atherosclerosis and was inversely linked to disease progression in patients with the disease. Deletion of PGC-1α in bone marrow derived macrophages promoted, whilst over expression of the gene inhibited foam cell formation. Importantly, macrophage specific deletion of PGC-1α accelerated atherosclerosis in the LDLR(-/-) mouse in vivo. These novel data support a functional role for PGC-1α in atheroprotection.
authors: School of Biomolecular and Biomedical Science, UCD Conway Institute, UCD, Dublin, Ireland.
authors: Cathal
authors: C
authors: McCarthy
authors: Nora T
authors: NT
authors: Lieggi
authors: Denis
authors: D
authors: Barry
authors: Declan
authors: D
authors: Mooney
authors: Monica
authors: M
authors: de Gaetano
authors: William G
authors: WG
authors: James
authors: Sarah
authors: S
authors: McClelland
authors: Mary C
authors: MC
authors: Barry
authors: Laure
authors: L
authors: Escoubet-Lozach
authors: Andrew C
authors: AC
authors: Li
authors: Christopher K
authors: CK
authors: Glass
authors: Desmond J
authors: DJ
authors: Fitzgerald
authors: Orina
authors: O
authors: Belton
mesh_terms: D000818:Animals; D001011:Aorta / Q000503:physiopathology; D050197:Atherosclerosis / Q000503:physiopathology*; D002478:Cells, Cultured; D005487:Foam Cells / Q000187:drug effects*; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D044243:Linoleic Acids, Conjugated / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D044243:Linoleic Acids, Conjugated; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C485290:Ppargc1a protein, mouse; D014157:Transcription Factors
keywords: PGC-1α; atherosclerosis regression; conjugated linoleic acid; foam cell formation
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