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Cardioprotection by H2S engages a cGMP-dependent protein kinase G/phospholamban pathway

Sofia-Iris Bibli1, Ioanna Andreadou2, Athanasia Chatzianastasiou3

  • 1Faculty of Pharmacy, University of Athens, Panepistimiopolis, Zografou, Athens 15771, Greece.

Cardiovascular Research
|April 15, 2015
PubMed

Insights

Hydrogen sulfide (H2S) protects the heart via a cGMP/PKG/PLN pathway. This cardioprotective effect is species-specific, with nitric oxide playing a role in mice but not rabbits.

Area of Science:

  • Cardiovascular Physiology
  • Molecular Cardiology
  • Biochemistry

Background:

  • Hydrogen sulfide (H2S) is recognized for its cardioprotective properties.
  • The precise molecular mechanisms underlying H2S-mediated cardioprotection in vivo are not fully elucidated.
  • Understanding these pathways is crucial for developing novel therapeutic strategies against myocardial injury.

Purpose of the Study:

  • To investigate the role of cyclic guanosine monophosphate (cGMP)-regulated pathways in H2S-induced infarct limitation.
  • To determine the contribution of specific signaling molecules, such as protein kinase G (PKG) and phospholamban (PLN), to H2S cardioprotection.
  • To assess the species-specific differences in H2S-mediated cardioprotection, particularly concerning the involvement of nitric oxide (NO).

Main Methods:

  • Myocardial ischemia/reperfusion (I/R) injury was induced in anesthetized rabbits and mice.
  • Animals were treated with sodium hydrosulfide (NaHS), a H2S donor, or vehicle.
  • Pharmacological inhibitors of cGMP-dependent protein kinase (PKG-I), KATP channels, and endothelial nitric oxide synthase (eNOS) were used.
  • Western blotting was employed to assess protein phosphorylation.
  • Studies were conducted in wild-type and PLN knockout (PLN KO) mice.

Main Results:

  • Sodium hydrosulfide (NaHS) administration significantly reduced infarct size in rabbits and increased cardiac cGMP levels.
  • The protective effect of NaHS in rabbits was abrogated by a PKG-I inhibitor but not by an l-NAME control.
  • NaHS enhanced phospholamban (PLN) phosphorylation in a PKG-dependent manner, and cardioprotection was lost in PLN KO mice.
  • In contrast to rabbits, the infarct-limiting effect of NaHS in mice was abolished by eNOS inhibition, indicating a species-specific role for NO.

Conclusions:

  • Cardioprotection induced by NaHS is mediated through a cGMP/PKG/PLN signaling cascade.
  • The involvement of nitric oxide in H2S-induced cardioprotection is species-dependent.
  • These findings highlight a conserved cGMP/PKG/PLN pathway but divergent roles of NO in H2S cardioprotection across species.
Abstract

Keywords:
H2SIschaemiaPhospholambanPostconditioningcGMP

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