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Updated: Jul 6, 2026
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Screening Assays to Characterize Novel Endothelial Regulators Involved in the Inflammatory Response
Published on: September 15, 2017
PPARdelta regulates multiple proinflammatory pathways to suppress atherosclerosis
Grant D Barish1, Annette R Atkins, Michael Downes
1Howard Hughes Medical Institute, Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
Summary
Peroxisome proliferator-activated receptor delta (PPARdelta) agonists reduce atherosclerosis in mice. PPARdelta activation lowers HDL cholesterol and suppresses inflammation, suggesting it as a therapeutic target for vascular disease.
Area of Science:
- Cardiovascular Research
- Molecular Biology
- Pharmacology
Background:
- Atherosclerosis involves lipid-laden macrophages and inflammation.
- Nuclear receptor PPARdelta influences lipid metabolism and macrophage inflammation.
- The therapeutic potential of PPARdelta in vascular disease remains unclear.
Purpose of the Study:
- To investigate the role of PPARdelta as a therapeutic target in atherosclerosis.
- To determine the effects of PPARdelta agonists on atherosclerotic lesion progression in vivo.
Main Methods:
- Utilized apolipoprotein E-deficient (apoE(-/-)) mice models.
- Administered orally active PPARdelta agonists.
- Conducted metabolic studies and gene expression analysis.
- Assessed monocyte transmigration and macrophage inflammatory responses.
Main Results:
- PPARdelta agonists significantly reduced atherosclerosis in apoE(-/-) mice.
- PPARdelta activation increased HDL levels and exerted anti-inflammatory effects within the vessel wall.
- PPARdelta suppressed chemokine signaling and induced Regulator of G protein signaling (RGS) genes.
- PPARdelta ligands inhibited monocyte transmigration and macrophage inflammatory responses.
Conclusions:
- PPARdelta antagonizes multiple pro-inflammatory pathways implicated in atherogenesis.
- PPARdelta-selective drugs show promise as a novel therapeutic strategy for atherosclerosis.
- Targeting PPARdelta may offer a dual approach to combatting vascular disease by modulating lipid homeostasis and inflammation.
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