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In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
08:22

In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model

Published on: October 27, 2020

Cardioprotection by adaptation to ischaemia augments autophagy in association with BAG-1 protein

Narasimman Gurusamy1, Istvan Lekli, Nikolai V Gorbunov

  • 1Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, 06030-1110, USA.

Journal of Cellular and Molecular Medicine
|September 17, 2008
PubMed

Insights

Myocardial adaptation protects the heart from ischemia by upregulating autophagy, a cellular recycling process. This protection involves the Bcl-2-associated athanogene (BAG-1) protein, which interacts with autophagy markers like LC3-II.

Area of Science:

  • Cardiovascular Biology
  • Cellular Biology
  • Molecular Medicine

Background:

  • Autophagy, a cellular degradation pathway, is implicated in cardiac diseases but its precise role and regulation remain unclear.
  • Bcl-2-associated athanogene (BAG-1) is a known pro-survival protein that interacts with heat shock proteins.
  • Myocardial adaptation to ischemia-reperfusion (I/R) injury is a recognized protective phenomenon.

Purpose of the Study:

  • To investigate the role of autophagy and BAG-1 in myocardial adaptation to ischemic injury.
  • To elucidate the molecular mechanisms underlying the cardioprotective effects of ischemic preconditioning.

Main Methods:

  • Utilized a rat model of lethal ischemia-reperfusion (I/R) with prior ischemic adaptation.
  • Employed electron microscopy to identify autophagosome structures.
  • Performed co-immunoprecipitation and co-immunofluorescence to assess protein interactions.
  • Used Wortmannin to inhibit autophagy and BAG-1 siRNA to block BAG-1 function.
  • Investigated hypoxic adaptation in cardiac myoblast cells.

Main Results:

  • Ischemic adaptation increased the expression of autophagy markers LC3-II and Beclin-1, and BAG-1.
  • Autophagosome structures were observed in adapted myocardium.
  • LC3-II was found to be bound with BAG-1.
  • Autophagy inhibition with Wortmannin abolished adaptation-induced increases in LC3-II, Beclin-1, BAG-1, and cardioprotection.
  • BAG-1 siRNA treatment attenuated LC3-II induction and abolished cardioprotection.
  • Hypoxic adaptation in cardiac cells increased LC3-II and BAG-1, effects reversed by BAG-1 siRNA, which also abolished improved cell survival.

Conclusions:

  • Myocardial protection induced by ischemic adaptation is, in part, mediated by the upregulation of autophagy.
  • The Bcl-2-associated athanogene (BAG-1) protein plays a crucial role in this adaptive cardioprotection by associating with autophagy.
  • Targeting the autophagy-BAG-1 pathway may offer novel therapeutic strategies for preventing cardiac ischemic injury.

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