
Cardioprotection by H2S engages a cGMP-dependent protein kinase G/phospholamban pathway
- Author
- Sofia-Iris Bibli, Ioanna Andreadou, Athanasia Chatzianastasiou, Christos Tzimas, Despina Sanoudou, Evangelia Kranias, Peter Brouckaert (UGent) , Ciro Coletta, Csaba Szabo, Dimitrios T Kremastinos, Efstathios K Iliodromitis and Andreas Papapetropoulos
- Organization
- 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 K-ATP channel inhibitor, glibenclamide, partially reversed the effects of NaHS, whereas inhibition of mitochondrial K-ATP 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 KOmice. 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, Postconditioning, Ischaemia, H2S, Phospholamban, ISCHEMIA-REPERFUSION INJURY, NITRIC-OXIDE SYNTHASE, K-ATP CHANNELS, PERMEABILITY TRANSITION PORE, ENDOGENOUS HYDROGEN-SULFIDE, PHOSPHOLAMBAN PHOSPHORYLATION, CYCLIC-GMP, SARCOPLASMIC-RETICULUM, HEART-FAILURE, PORCINE MODEL
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-6970702
- MLA
- Bibli, Sofia-Iris et al. “Cardioprotection by H2S Engages a cGMP-dependent Protein Kinase G/phospholamban Pathway.” CARDIOVASCULAR RESEARCH 106.3 (2015): 432–442. Print.
- APA
- Bibli, S.-I., Andreadou, I., Chatzianastasiou, A., Tzimas, C., Sanoudou, D., Kranias, E., Brouckaert, P., et al. (2015). Cardioprotection by H2S engages a cGMP-dependent protein kinase G/phospholamban pathway. CARDIOVASCULAR RESEARCH, 106(3), 432–442.
- Chicago author-date
- Bibli, Sofia-Iris, Ioanna Andreadou, Athanasia Chatzianastasiou, Christos Tzimas, Despina Sanoudou, Evangelia Kranias, Peter Brouckaert, et al. 2015. “Cardioprotection by H2S Engages a cGMP-dependent Protein Kinase G/phospholamban Pathway.” Cardiovascular Research 106 (3): 432–442.
- Chicago author-date (all authors)
- Bibli, Sofia-Iris, Ioanna Andreadou, Athanasia Chatzianastasiou, Christos Tzimas, Despina Sanoudou, Evangelia Kranias, Peter Brouckaert, Ciro Coletta, Csaba Szabo, Dimitrios T Kremastinos, Efstathios K Iliodromitis, and Andreas Papapetropoulos. 2015. “Cardioprotection by H2S Engages a cGMP-dependent Protein Kinase G/phospholamban Pathway.” Cardiovascular Research 106 (3): 432–442.
- Vancouver
- 1.Bibli S-I, Andreadou I, Chatzianastasiou A, Tzimas C, Sanoudou D, Kranias E, et al. Cardioprotection by H2S engages a cGMP-dependent protein kinase G/phospholamban pathway. CARDIOVASCULAR RESEARCH. 2015;106(3):432–42.
- IEEE
- [1]S.-I. Bibli et al., “Cardioprotection by H2S engages a cGMP-dependent protein kinase G/phospholamban pathway,” CARDIOVASCULAR RESEARCH, vol. 106, no. 3, pp. 432–442, 2015.
@article{6970702, 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 K-ATP channel inhibitor, glibenclamide, partially reversed the effects of NaHS, whereas inhibition of mitochondrial K-ATP 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 KOmice. 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.}, author = {Bibli, Sofia-Iris and Andreadou, Ioanna and Chatzianastasiou, Athanasia and Tzimas, Christos and Sanoudou, Despina and Kranias, Evangelia and Brouckaert, Peter and Coletta, Ciro and Szabo, Csaba and Kremastinos, Dimitrios T and Iliodromitis, Efstathios K and Papapetropoulos, Andreas}, issn = {0008-6363}, journal = {CARDIOVASCULAR RESEARCH}, keywords = {cGMP,Postconditioning,Ischaemia,H2S,Phospholamban,ISCHEMIA-REPERFUSION INJURY,NITRIC-OXIDE SYNTHASE,K-ATP CHANNELS,PERMEABILITY TRANSITION PORE,ENDOGENOUS HYDROGEN-SULFIDE,PHOSPHOLAMBAN PHOSPHORYLATION,CYCLIC-GMP,SARCOPLASMIC-RETICULUM,HEART-FAILURE,PORCINE MODEL}, language = {eng}, number = {3}, pages = {432--442}, title = {Cardioprotection by H2S engages a cGMP-dependent protein kinase G/phospholamban pathway}, url = {http://dx.doi.org/10.1093/cvr/cvv129}, volume = {106}, year = {2015}, }
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