PPARγ as an indicator of vascular function in an experimental model of metabolic syndrome in rabbits

Atherosclerosis. 2021 Sep:332:16-23. doi: 10.1016/j.atherosclerosis.2021.08.006. Epub 2021 Aug 5.

Abstract

Background and aims: Underlying mechanisms associated with vascular dysfunction in metabolic syndrome (MetS) remain unclear and can even vary from one vascular bed to another.

Methods: In this study, MetS was induced by a high-fat, high-sucrose diet, and after 28 weeks, aorta and renal arteries were removed and used for isometric recording of tension in organ baths, protein expression by Western blot, and histological analysis to assess the presence of atherosclerosis.

Results: MetS induced a mild hypertension, pre-diabetes, central obesity and dyslipidaemia. Our results indicated that MetS did not change the contractile response in either the aorta or renal artery. Conversely, vasodilation was affected in both arteries in a different way. The aorta from MetS showed vascular dysfunction, including lower response to acetylcholine and sodium nitroprusside, while the renal artery from MetS presented a preserved relaxation to acetylcholine and an increased sensitivity to sodium nitroprusside. We did not find vascular oxidative stress in the aorta from MetS, but we found a significant decrease in PPARγ, phospho-Akt (p-Akt) and phospho-eNOS (p-eNOS) protein expression. On the other hand, we found oxidative stress in the renal artery from MetS, and PPARγ, Akt and p-Akt were overexpressed. No evidence of atherosclerosis was found in arteries from MetS.

Conclusions: MetS affects vascular function differently depending on the vessel. In the aorta, it decreases both the vasodilation and the expression of the PPARγ/Akt/eNOS pathway, while in the renal artery, it increases the expression of PPARγ/Akt signalling pathway without decreasing the vasodilation.

Keywords: Akt; Metabolic syndrome; PPARγ; Vascular dysfunction; Vascular oxidative stress; eNOS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Endothelium, Vascular
  • Metabolic Syndrome*
  • Models, Theoretical
  • Nitric Oxide Synthase Type III
  • PPAR gamma
  • Proto-Oncogene Proteins c-akt
  • Rabbits
  • Vasodilation

Substances

  • PPAR gamma
  • Nitric Oxide Synthase Type III
  • Proto-Oncogene Proteins c-akt