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

    40 Citations (Scopus)

    Abstract

    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
    Volume106
    Issue number3
    DOIs
    StatePublished - Jun 1 2015

    Fingerprint

    Cyclic GMP-Dependent Protein Kinases
    Cyclic GMP-Dependent Protein Kinase Type I
    phospholamban
    sodium bisulfide
    Rabbits
    KATP Channels
    Glyburide
    Nitroarginine
    Reperfusion
    Myocardial Ischemia
    Nitric Oxide
    Esters
    Phosphorylation
    Pharmacology

    Keywords

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

    ASJC Scopus subject areas

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

    Cite this

    Cardioprotection by H<inf>2</inf>S engages a cGMP-dependent protein kinase G/phospholamban pathway. / Bibli, Sofia Iris; Andreadou, Ioanna; Chatzianastasiou, Athanasia; Tzimas, Christos; Sanoudou, Despina; Kranias, Evangelia; Brouckaert, Peter; Coletta, Ciro; Szabo, Csaba; Kremastinos, Dimitrios Th; Iliodromitis, Efstathios K.; Papapetropoulos, Andreas.

    In: Cardiovascular Research, Vol. 106, No. 3, 01.06.2015, p. 432-442.

    Research output: Contribution to journalArticle

    Bibli, SI, Andreadou, I, Chatzianastasiou, A, Tzimas, C, Sanoudou, D, Kranias, E, Brouckaert, P, Coletta, C, Szabo, C, Kremastinos, DT, Iliodromitis, EK & Papapetropoulos, A 2015, 'Cardioprotection by H<inf>2</inf>S engages a cGMP-dependent protein kinase G/phospholamban pathway', Cardiovascular Research, vol. 106, no. 3, pp. 432-442. https://doi.org/10.1093/cvr/cvv129
    Bibli SI, Andreadou I, Chatzianastasiou A, Tzimas C, Sanoudou D, Kranias E et al. Cardioprotection by H<inf>2</inf>S engages a cGMP-dependent protein kinase G/phospholamban pathway. Cardiovascular Research. 2015 Jun 1;106(3):432-442. https://doi.org/10.1093/cvr/cvv129
    Bibli, Sofia Iris ; Andreadou, Ioanna ; Chatzianastasiou, Athanasia ; Tzimas, Christos ; Sanoudou, Despina ; Kranias, Evangelia ; Brouckaert, Peter ; Coletta, Ciro ; Szabo, Csaba ; Kremastinos, Dimitrios Th ; Iliodromitis, Efstathios K. ; Papapetropoulos, Andreas. / Cardioprotection by H<inf>2</inf>S engages a cGMP-dependent protein kinase G/phospholamban pathway. In: Cardiovascular Research. 2015 ; Vol. 106, No. 3. pp. 432-442.
    @article{66d40c23d96b4d0a85f91dcf3df637bb,
    title = "Cardioprotection by H2S engages a cGMP-dependent protein kinase G/phospholamban pathway",
    abstract = "Aims: H2S 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 H2S in vivo. Methods and results: Anaesthetized rabbits were subjected to myocardial ischaemia (I)/reperfusion (R), and infarct size was determined in control or H2S-exposed groups. The H2S donor sodium hydrosulfide (NaHS, an agent that generates H2S) 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 KATP channel inhibitor, glibenclamide, partially reversed the effects of NaHS, whereas inhibition of mitochondrial KATP 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 H2S-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 H2S response is species-specific.",
    keywords = "cGMP, H<inf>2</inf>S, Ischaemia, Phospholamban, Postconditioning",
    author = "Bibli, {Sofia Iris} and Ioanna Andreadou and Athanasia Chatzianastasiou and Christos Tzimas and Despina Sanoudou and Evangelia Kranias and Peter Brouckaert and Ciro Coletta and Csaba Szabo and Kremastinos, {Dimitrios Th} and Iliodromitis, {Efstathios K.} and Andreas Papapetropoulos",
    year = "2015",
    month = "6",
    day = "1",
    doi = "10.1093/cvr/cvv129",
    language = "English (US)",
    volume = "106",
    pages = "432--442",
    journal = "Cardiovascular Research",
    issn = "0008-6363",
    publisher = "Oxford University Press",
    number = "3",

    }

    TY - JOUR

    T1 - Cardioprotection by H2S engages a cGMP-dependent protein kinase G/phospholamban pathway

    AU - Bibli, Sofia Iris

    AU - Andreadou, Ioanna

    AU - Chatzianastasiou, Athanasia

    AU - Tzimas, Christos

    AU - Sanoudou, Despina

    AU - Kranias, Evangelia

    AU - Brouckaert, Peter

    AU - Coletta, Ciro

    AU - Szabo, Csaba

    AU - Kremastinos, Dimitrios Th

    AU - Iliodromitis, Efstathios K.

    AU - Papapetropoulos, Andreas

    PY - 2015/6/1

    Y1 - 2015/6/1

    N2 - Aims: H2S 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 H2S in vivo. Methods and results: Anaesthetized rabbits were subjected to myocardial ischaemia (I)/reperfusion (R), and infarct size was determined in control or H2S-exposed groups. The H2S donor sodium hydrosulfide (NaHS, an agent that generates H2S) 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 KATP channel inhibitor, glibenclamide, partially reversed the effects of NaHS, whereas inhibition of mitochondrial KATP 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 H2S-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 H2S response is species-specific.

    AB - Aims: H2S 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 H2S in vivo. Methods and results: Anaesthetized rabbits were subjected to myocardial ischaemia (I)/reperfusion (R), and infarct size was determined in control or H2S-exposed groups. The H2S donor sodium hydrosulfide (NaHS, an agent that generates H2S) 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 KATP channel inhibitor, glibenclamide, partially reversed the effects of NaHS, whereas inhibition of mitochondrial KATP 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 H2S-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 H2S response is species-specific.

    KW - cGMP

    KW - H<inf>2</inf>S

    KW - Ischaemia

    KW - Phospholamban

    KW - Postconditioning

    UR - http://www.scopus.com/inward/record.url?scp=84930338644&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84930338644&partnerID=8YFLogxK

    U2 - 10.1093/cvr/cvv129

    DO - 10.1093/cvr/cvv129

    M3 - Article

    VL - 106

    SP - 432

    EP - 442

    JO - Cardiovascular Research

    JF - Cardiovascular Research

    SN - 0008-6363

    IS - 3

    ER -