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Hydroxychloroquine Protects against Cardiac Ischaemia/Reperfusion Injury In Vivo via Enhancement of ERK1/2 Phosphorylation

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Listed:
  • Lauren Bourke
  • James McCormick
  • Valerie Taylor
  • Charis Pericleous
  • Benoit Blanchet
  • Nathalie Costedoat-Chalumeau
  • Daniel Stuckey
  • Mark F Lythgoe
  • Anastasis Stephanou
  • Yiannis Ioannou

Abstract

An increasing number of investigations including human studies demonstrate that pharmacological ischaemic preconditioning is a viable way to protect the heart from myocardial ischaemia/reperfusion (I/R) injury. This study investigated the role of hydroxychloroquine (HCQ) in the heart during I/R injury. In vitro and in vivo models of myocardial I/R injury were used to assess the effects of HCQ. It was found that HCQ was protective in neonatal rat cardiomyocytes through inhibition of apoptosis, measured by TUNEL and cleaved caspase-3. This protection in vitro was mediated through enhancement of ERK1/2 phosphorylation mediated by HCQ in a dose-dependent fashion. A decrease in infarct size was observed in an in vivo model of myocardial I/R injury in HCQ treated animals and furthermore this protection was blocked in the presence of the ERK1/2 inhibitor U0126. For the first time, we have shown that HCQ promotes a preconditioning like protection in an in vivo simulated rat myocardial I/R injury model. Moreover, it was shown that HCQ is protective via enhanced phosphorylation of the pro-survival kinase ERK1/2.

Suggested Citation

  • Lauren Bourke & James McCormick & Valerie Taylor & Charis Pericleous & Benoit Blanchet & Nathalie Costedoat-Chalumeau & Daniel Stuckey & Mark F Lythgoe & Anastasis Stephanou & Yiannis Ioannou, 2015. "Hydroxychloroquine Protects against Cardiac Ischaemia/Reperfusion Injury In Vivo via Enhancement of ERK1/2 Phosphorylation," PLOS ONE, Public Library of Science, vol. 10(12), pages 1-14, December.
    • Handle: RePEc:plo:pone00:0143771
    DOI: 10.1371/journal.pone.0143771
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    References listed on IDEAS

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    1. Nuria Martinez-Lopez & Diana Athonvarangkul & Priti Mishall & Srabani Sahu & Rajat Singh, 2013. "Autophagy proteins regulate ERK phosphorylation," Nature Communications, Nature, vol. 4(1), pages 1-14, December.
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