PPARalpha, but not PPARgamma, activators decrease macrophage-laden atherosclerotic lesions in a nondiabetic mouse...

Area of Science:

• Cardiovascular Research
• Metabolic Disease Research
• Pharmacology

Background:

• Atherosclerosis involves lipid-laden macrophages in arterial walls.
• Nuclear receptors Peroxisome proliferator-activated receptor (PPAR) alpha and gamma may influence atherogenesis.
• PPARs modulate macrophage function, suggesting ligands could impact atherosclerosis via direct effects.

Purpose of the Study:

• To investigate the effects of PPAR alpha (fenofibrate) and PPAR gamma (rosiglitazone, pioglitazone) ligands on atherogenesis.
• To determine if PPAR ligands modulate macrophage foam cell formation in a dyslipidemic murine model.

Main Methods:

• Dyslipidemic, non-diabetic mice were fed a Western diet with or without fenofibrate, rosiglitazone, or pioglitazone for 10 weeks.
• Atherosclerotic lesion development, lipid accumulation, and macrophage content were assessed.
• Metabolic parameters including lipoprotein metabolism and insulin sensitivity were measured.

Main Results:

• Fenofibrate improved lipoprotein metabolism but not insulin sensitivity.
• Rosiglitazone and pioglitazone improved glucose homeostasis but not lipoprotein metabolism.
• Fenofibrate significantly reduced lipid and macrophage accumulation in aortic sinus lesions; rosiglitazone and pioglitazone did not.

Conclusions:

• PPAR alpha activation protects against macrophage foam cell formation in this model.
• PPAR gamma activation did not demonstrate protective effects on lesion development or macrophage content.
• PPAR alpha ligands may be beneficial in preventing early atherosclerotic lesion progression.