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PPARβ down-regulation is involved in high glucose-induced endothelial injury via acceleration of nitrative stress

Chuang Yang1, Lai Xue2, Yang Wu3

  • 1Department of Pharmacology, Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Key Laboratory of Drug Metabolism, College of Pharmacy, Chongqing Medical University, Chongqing 400016, PR China.

Microvascular Research
|October 26, 2021
PubMed

Insights

High glucose impairs blood vessel function by reducing Peroxisome proliferator-activated receptor beta (PPARβ) and nitric oxide (NO) production. Activating PPARβ with GW0742 protects against this damage, suggesting a therapeutic target for diabetic vascular disease.

Area of Science:

  • Vascular Biology
  • Endocrinology
  • Diabetology

Background:

  • Endothelial injury is central to diabetic vascular complications.
  • Peroxisome proliferator-activated receptor beta (PPARβ) is implicated in diabetes mellitus (DM) and its complications.
  • The precise molecular mechanisms of PPARβ in DM-induced endothelial dysfunction require further elucidation.

Purpose of the Study:

  • To investigate the role of PPARβ in high glucose-induced endothelial dysfunction.
  • To explore the relationship between PPARβ, nitric oxide (NO) production, and nitrative stress in diabetic conditions.
  • To evaluate the therapeutic potential of PPARβ activation in mitigating endothelial damage.

Main Methods:

  • Rat aortic rings were incubated under high glucose conditions.
  • Expression levels of PPARβ, endothelial nitric oxide synthase (eNOS), and inducible nitric oxide synthase (iNOS) were measured at mRNA and protein levels.
  • Nitric oxide (NO) and 3-nitrotyrosine concentrations were assessed.
  • The effects of GW0742 (PPARβ agonist), GSK0660 (PPARβ antagonist), and N-G-nitro-L-arginine methyl ester (NOS inhibitor) were evaluated.

Main Results:

  • High glucose impaired endothelium-dependent relaxation and endothelial structure.
  • High glucose significantly decreased PPARβ and eNOS expression while increasing iNOS and 3-nitrotyrosine.
  • Reduced NO concentration was observed under high glucose conditions.
  • GW0742 treatment reversed high glucose-induced endothelial dysfunction.
  • GSK0660 and NOS inhibition counteracted the protective effects of GW0742.

Conclusions:

  • High glucose-induced endothelial dysfunction in rat aorta involves the down-regulation of PPARβ, potentially mediated by nitrative stress.
  • PPARβ activation demonstrates protective effects against high glucose-induced endothelial damage.
  • Targeting the PPARβ-nitrative stress pathway may offer a novel therapeutic strategy for diabetic vascular complications.
Keywords:
Diabetes mellitusDysfunctionEndotheliumHigh glucoseNitrative stressPPARβ

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