The ligands/activators for peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma increase...

Area of Science:

• Endothelial cell biology
• Molecular pharmacology
• Oxidative stress research

Background:

• Endothelial cells play a crucial role in vascular health.
• Oxidative stress, mediated by enzymes like NADPH oxidase, contributes to endothelial dysfunction.
• Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors involved in various cellular processes.

Purpose of the Study:

• To investigate the impact of peroxisome proliferator-activated receptor (PPAR) ligands on antioxidant and pro-oxidant enzyme expression in human endothelial cells.
• To determine the specific roles of PPARalpha and PPARgamma in regulating Cu2+,Zn2+-superoxide dismutase (CuZn-SOD) and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase.

Main Methods:

• Primary cultures of human umbilical vein endothelial cells (HUVEC) and human aorta endothelial cells (HAEC) were utilized.
• Cells were treated with various PPAR ligands/activators, including bezafibrate, troglitazone, and pioglitazone.
• Gene and protein expression levels of CuZn-SOD, NADPH oxidase subunits (p22phox, p47phox), and PPARs were analyzed.

Main Results:

• PPARalpha, PPARbeta/delta/Nuc1, and PPARgamma were detected in endothelial cells.
• PPARalpha activation (bezafibrate) increased CuZn-SOD expression.
• PPARgamma activation (troglitazone, pioglitazone) upregulated PPARalpha and CuZn-SOD expression.
• Fatty acid treatment showed a positive correlation between CuZn-SOD and PPARalpha mRNA levels.
• PPARalpha and PPARgamma activators reduced NADPH oxidase subunit expression (p22phox, p47phox).

Conclusions:

• PPARalpha and PPARgamma are expressed in endothelial cells and modulate key enzymes involved in oxidative stress.
• Activation of PPARalpha and PPARgamma enhances antioxidant capacity by increasing CuZn-SOD.
• PPAR activation suppresses NADPH oxidase activity, potentially mitigating oxidative damage in endothelial cells.
• These findings suggest a physiological role for PPARs as radical scavengers in the endothelium.