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

39 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
Pages (from-to)432-442
Number of pages11
JournalCardiovascular Research
Volume106
Issue number3
DOIs
Publication statusPublished - 1 Jun 2015
Externally publishedYes

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

Bibli, S. I., Andreadou, I., Chatzianastasiou, A., Tzimas, C., Sanoudou, D., Kranias, E., ... 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. https://doi.org/10.1093/cvr/cvv129

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.
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AU - Tzimas, Christos

AU - Sanoudou, Despina

AU - Kranias, Evangelia

AU - Brouckaert, Peter

AU - Coletta, Ciro

AU - Szabo, Csaba

AU - Kremastinos, Dimitrios Th

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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.

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