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

    Research output: Contribution to journalArticle

    48 Scopus citations


    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 (US)
    Pages (from-to)432-442
    Number of pages11
    JournalCardiovascular Research
    Issue number3
    StatePublished - Jun 1 2015


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

    ASJC Scopus subject areas

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

    Fingerprint Dive into the research topics of 'Cardioprotection by H<inf>2</inf>S engages a cGMP-dependent protein kinase G/phospholamban pathway'. Together they form a unique fingerprint.

  • 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.