Modulatory Role of SIRT1 and Resistin as Therapeutic Targets in Patients with Aortic Valve Stenosis

Arch Med Res. 2019 Aug;50(6):333-341. doi: 10.1016/j.arcmed.2019.10.001. Epub 2019 Oct 31.

Abstract

Background: Inflammatory is one of the main cause of aortic valve stenosis (AS), so discovering novel biomarkers for the targeted therapy of inflammation could be an attractive strategy in AS prevention. The objectives of our study were to clarify the modulatory role of resistin and silent information regulator 1 (SIRT1) before and after surgery and also to evaluate the therapeutic effects of resveratrol.

Methods: Nineteen AS patients and 15 healthy subjects were studied as the case and control groups, respectively. Peripheral blood mononuclear cells (PBMCs) were isolated and cultured to determine the levels of resistin and SIRT1 and the effects of resveratrol on them.

Results: Significant increase in resistin expression was observed in the patients compare to the control (p ≤0.01), and this upregulation was augmented 72 h following surgery (p ≤0.01). The SIRT1 expression decreased in the AS group compare to the control but this reduction was not significant. Aortic valve replacement caused a higher decrease in the protein (p ≤0.01) and mRNA level (p ≤0.05) of SIRT1. Resveratrol in the AS group significantly diminished the resistin level (p ≤0.05) but increased the SIRT1 level (p ≤0.001).

Conclusions: In our patients with AS, the resistin level was increased, whereas the expression of SIRT1 was reduced and surgery augmented these alterations. Resveratrol improved inflammation in the PBMCs of the patients through the SIRT1/resistin pathway. These findings suggest that pharmacological therapy with resveratrol might be a novel approach to alleviating inflammation in patients with AS.

Keywords: Antioxidant; Aortic valve stenosis; Cytokine; Inflammation; Resistin; Resveratrol; Sirtuin1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Aortic Valve Stenosis / therapy*
  • Biomarkers / analysis
  • Enzyme Inhibitors / therapeutic use*
  • Female
  • Humans
  • Inflammation / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • RNA, Messenger / metabolism
  • Resistin / metabolism*
  • Resveratrol / therapeutic use*
  • Sirtuin 1 / metabolism*
  • Stilbenes
  • Up-Regulation / drug effects

Substances

  • Biomarkers
  • Enzyme Inhibitors
  • RETN protein, human
  • RNA, Messenger
  • Resistin
  • Stilbenes
  • SIRT1 protein, human
  • Sirtuin 1
  • Resveratrol