Differential inhibition of macrophage foam-cell formation and atherosclerosis in mice by PPARalpha, beta/delta, and gamma
- 1Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0682, USA. acli@ucsd.edu
- 0Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093-0682, USA. acli@ucsd.edu
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View abstract on PubMed
Summary
This summary is machine-generated.Peroxisome proliferator-activated receptors (PPARs) alpha and gamma inhibit atherosclerosis by distinct pathways. PPARalpha and PPARgamma agonists reduce foam cell formation, offering potential therapeutic targets for cardiovascular disease.
Area Of Science
- Biochemistry
- Molecular Biology
- Cardiovascular Research
Background
- Peroxisome proliferator-activated receptors (PPARs) regulate lipid metabolism and inflammation.
- In vitro studies suggest PPARs have antiatherogenic effects by modulating cholesterol efflux and inflammation.
- The in vivo relevance of these PPAR activities in atherosclerosis remains to be fully elucidated.
Purpose Of The Study
- To investigate the in vivo effects of PPARalpha, beta/delta, and gamma agonists on foam cell formation and atherosclerosis.
- To determine the specific mechanisms by which PPAR agonists impact macrophage cholesterol homeostasis.
Main Methods
- Utilized male LDL receptor-deficient (LDLR(-/-)) mice as an atherosclerosis model.
- Administered specific agonists for PPARalpha, PPARbeta/delta, and PPARgamma.
- Analyzed effects on atherosclerosis progression and macrophage foam cell formation in vivo.
Main Results
- PPARalpha and PPARgamma agonists significantly inhibited atherosclerosis and foam cell formation.
- PPARbeta/delta agonist failed to inhibit lesion formation.
- PPARalpha and PPARgamma agonists acted through distinct, ABCA1-independent pathways to inhibit foam cell formation.
- PPARalpha's effect required Liver X Receptors (LXRs), while PPARgamma's effect involved reduced cholesterol esterification and ABCG1 induction.
Conclusions
- PPARalpha and PPARgamma agonists demonstrate significant antiatherogenic potential through distinct mechanisms.
- PPARs influence macrophage cholesterol homeostasis via receptor-specific pathways.
- These findings suggest potential pharmacological strategies targeting PPARs for atherosclerosis treatment.
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