Heat Shock Prevents Insulin Resistance Induced Vascular Complications By Augmenting Angiotensin-(1-7) Signalling

  1. Kulbhushan Tikoo
  1. Department of Pharmacology and Toxicology, National Institute of Pharmaceutical Education and Research, S.A.S. Nagar (Mohali), Punjab-160062, India
  1. Corresponding Author: Kulbhushan Tikoo, Email: tikoo.k{at}gmail.com

Abstract

We have investigated the role of heat shock (HS) in preventing insulin resistance induced endothelial dysfunction. To best of our knowledge here we report for the first time that insulin resistance inhibits vascular HSP72 expression. Heat shock treatment (HS, 41°C for 20 min) restored the HSP72 expression. High fat diet (HFD) fed insulin resistant rats show attenuated Ang-(1-7) induced vasodilator effect, eNOS phosphorylation, AMPK phosphorylation and SIRT1 expression. Interestingly, HS prevented this attenuation. We also provide first evidence that HFD fed rats show increased vascular DNMT1 expression and HS prevented this increase. Our data shows that in HFD fed rats HS prevented loss in the expression of Ang-(1-7) receptor Mas and ACE2 responsible for vascular complications. Further, inhibition of eNOS (L-NAME), Mas (A-779) and SIRT1 (Nicotinamide) prevented the favourable effects of HS. This suggests that HS augmented Ang-(1-7) signalling via Mas/eNOS/SIRT1 pathway. Our study, for the first time, suggests that induction of intracellular HSP72 alters DNMT1 expression and may function as epigenetic regulator of SIRT1 and eNOS expression. We propose that induction of HSP72 is a novel approach to prevent insulin resistance induced vascular complications.

  • Received August 20, 2013.
  • Accepted November 14, 2013.

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