Macrophage PPAR gamma Co‐activator‐1 alpha participates in repressing foam cell formation and atherosclerosis in response to conjugated linoleic acid. Issue 9 (21st August 2013)

• Record Type: Journal Article
• Authors: McCarthy, Cathal; Lieggi, Nora T.; Barry, Denis; Mooney, Declan; de Gaetano, Monica; James, William G.; McClelland, Sarah; Barry, Mary C.; Escoubet‐Lozach, Laure; Li, Andrew C.; Glass, Christopher K; Fitzgerald, Desmond J.; Belton, Orina
• Is Part Of: EMBO molecular medicine. Volume 5:Issue 9(2013:Sep.)
• Page Start: 1443
• Page End: 1457
• Publication Date: 2013-08-21
• Subjects: Molecular biology -- Periodicals; Medical genetics -- Periodicals; Pathology, Molecular -- Periodicals; 616.04205
• DOI: 10.1002/emmm.201302587
• Languages: English
• ISSNs: 1757-4676

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="emmm201302587-sec-0001" sec-type="section"> <p>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 <italic>in vivo</italic>. 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 <italic>in vivo</italic>. These novel data support a functional role for PGC‐1α in atheroprotection.</p> </sec> </abstract>