biostudies-literatureTakata YNIDDK NIH HHSHoward Hughes Medical InstituteNHLBI NIH HHS4277-82https://www.ebi.ac.uk/biostudies/studies/S-EPMC2393800biostudies-literatureUnknown105(11)Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor delta (PPARdelta) has been shown to improve insulin resistance, adiposity, and plasma HDL levels. However, its antiatherogenic role remains controversial. Here we report atheroprotective effects of PPARdelta activation in a model of angiotensin II (AngII)-accelerated atherosclerosis, characterized by increased vascular inflammation related to repression of an antiinflammatory corepressor, B cell lymphoma-6 (Bcl-6), and the regulators of G protein-coupled signaling (RGS) proteins RGS4 and RGS5. In this model, administration of the PPARdelta agonist GW0742 (1 or 10 mg/kg) substantially attenuated AngII-accelerated atherosclerosis without altering blood pressure and increased vascular expression of Bcl-6, RGProceedings of the National Academy of Sciences of the United States of AmericaPPARdelta-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis.PMC2393800R01 HL105278R37 DK057978P01 HL088093Liu JYin FLee CHAtkins ARLyon CJHsueh WATakata YCollins ARBarish GDTangirala RKDownes MEvans RMfalsePPARdelta-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis.Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor delta (PPARdelta) has been shown to improve insulin resistance, adiposity, and plasma HDL levels. However, its antiatherogenic role remains controversial. Here we report atheroprotective effects of PPARdelta activation in a model of angiotensin II (AngII)-accelerated atherosclerosis, characterized by increased vascular inflammation related to repression of an antiinflammatory corepressor, B cell lymphoma-6 (Bcl-6), and the regulators of G protein-coupled signaling (RGS) proteins RGS4 and RGS5. In this model, administration of the PPARdelta agonist GW0742 (1 or 10 mg/kg) substantially attenuated AngII-accelerated atherosclerosis without altering blood pressure and increased vascular expression of Bcl-6, RG2008-01-01T00:00:00Z2008 Mar2025-04-19T06:40:28.841Z2019-03-27T00:15:11ZS-EPMC23938001833749510.1073/pnas.0708647105