Cardioprotection by H<inf>2</inf>S engages a cGMP-dependent protein kinase G/phospholamban pathway

Sofia Iris Bibli, Ioanna Andreadou, Athanasia Chatzianastasiou, Christos Tzimas, Despina Sanoudou, Evangelia Kranias, Peter Brouckaert, Ciro Coletta, Csaba Szabo, Dimitrios Th Kremastinos, Efstathios K. Iliodromitis, Andreas Papapetropoulos

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42 Citations (Scopus)


Aims: H<inf>2</inf>S is known to confer cardioprotection; however, the pathways mediating its effects in vivo remain incompletely understood. The purpose of the present study is to evaluate the contribution of cGMP-regulated pathways in the infarct-limiting effect of H<inf>2</inf>S in vivo. Methods and results: Anaesthetized rabbits were subjected to myocardial ischaemia (I)/reperfusion (R), and infarct size was determined in control or H<inf>2</inf>S-exposed groups. The H<inf>2</inf>S donor sodium hydrosulfide (NaHS, an agent that generates H<inf>2</inf>S) increased cardiac cGMP and reduced the infarct size. The cGMP-dependent protein kinase (PKG)-I inhibitor DT2 abrogated the protective effect of NaHS, whereas the control peptide TAT or l-nitroarginine methyl ester (l-NAME) did not alter the effect of NaHS. Moreover, the K<inf>ATP</inf> channel inhibitor, glibenclamide, partially reversed the effects of NaHS, whereas inhibition of mitochondrial K<inf>ATP</inf> did not modify the NaHS response. NaHS enhanced phosphorylation of phospholamban (PLN), in a PKG-dependent manner. To further investigate the role of PLN in H<inf>2</inf>S-mediated cardioprotection, wild-type and PLN KO mice underwent I/R. NaHS did not exert cardioprotection in PLN KO mice. Unlike what was observed in rabbits, genetic or pharmacological inhibition of eNOS abolished the infarct-limiting effect of NaHS in mice. Conclusions: Our findings demonstrate (i) that administration of NaHS induces cardioprotection via a cGMP/PKG/PLN pathway and (ii) contribution of nitric oxide to the H<inf>2</inf>S response is species-specific.

Original languageEnglish
Pages (from-to)432-442
Number of pages11
JournalCardiovascular Research
Issue number3
Publication statusPublished - 1 Jun 2015
Externally publishedYes



  • cGMP
  • H<inf>2</inf>S
  • Ischaemia
  • Phospholamban
  • Postconditioning

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)
  • Physiology

Cite this

Bibli, S. I., Andreadou, I., Chatzianastasiou, A., Tzimas, C., Sanoudou, D., Kranias, E., Brouckaert, P., Coletta, C., Szabo, C., Kremastinos, D. T., Iliodromitis, E. K., & Papapetropoulos, A. (2015). Cardioprotection by H<inf>2</inf>S engages a cGMP-dependent protein kinase G/phospholamban pathway. Cardiovascular Research, 106(3), 432-442.