Interference with PPARγ in endothelium accelerates angiotensin II-induced endothelial dysfunction.

Area of Science:

• Cardiovascular Biology
• Endocrinology
• Molecular Medicine

Background:

• Endothelial peroxisome proliferator-activated receptor gamma (PPARγ) is crucial for vascular function and blood pressure regulation.
• Previous studies showed that impaired endothelial PPARγ leads to endothelial dysfunction and heightened pressor response to angiotensin II (ANG II).

Purpose of the Study:

• To investigate if interfering with endothelial PPARγ exacerbates ANG II-induced endothelial dysfunction.
• To elucidate the underlying mechanisms, focusing on oxidative stress and inflammatory pathways.

Main Methods:

• Utilized transgenic mice (E-V290M) with endothelial-specific dominant-negative PPARγ expression.
• Infused mice with a subpressor dose of ANG II or saline for 2 weeks.
• Assessed endothelial function via acetylcholine-induced responses in basilar and carotid arteries, and analyzed oxidative stress markers (superoxide, Nox2, Catalase, SOD3) and NF-κB activity.

Main Results:

• ANG II infusion impaired acetylcholine-induced vasodilation in E-V290M mice but not in wild-type (NT) mice, independent of blood pressure changes.
• Elevated superoxide levels and Nox2 expression, with decreased Catalase and SOD3, were observed in ANG II-infused E-V290M mice.
• Increased NF-κB activity was indicated by elevated p65 and decreased Iκ-Bα in the aorta of ANG II-infused E-V290M mice. Treatment with Tempol improved endothelial function.

Conclusions:

• Interference with endothelial PPARγ accelerates ANG II-mediated endothelial dysfunction in both cerebral and conduit arteries.
• The mechanism involves increased oxidative stress and NF-κB activation.
• Endothelial PPARγ plays a protective role against ANG II-induced endothelial dysfunction.