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

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

doi:10.1093/cvr/cvv129

Cited by 74 publications

(83 citation statements)

References 64 publications

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“…In contrast to Akt phosphorylation, we observed no significant increase in ERK1/2 phosphorylation at early reperfusion following postconditioning with GYY4137. It has been reported by others that a bolus dose of Na 2 S at reperfusion could activate ERK1/2 and also inhibit GSK-3β (Lambert et al, 2014, Li et al, 2015b, Bibli et al, 2015. However, since in our hands GSK-3β phosphorylation (leading to enzyme inhibition) by GYY4137 was abrogated by LY294002, this suggests it is downstream of PI3K/Akt, rather than ERK1/2.…”

Section: Gyy4137 Postconditioning Activates Pi3k/akt Signallingcontrasting

confidence: 44%

“…Bibli et al (2015) showed that a bolus dose of NaSH 10 minutes before reperfusion then continuous infusion of NaSH till the end of reperfusion was required to significantly exert cardioprotection in rabbit. In comparison with these results, in this study we showed that a single bolus dose of GYY4137 at reperfusion had a significant cardioprotective effect against myocardial infarction in the rat.…”

Section: Infarct Limitation By Gyy4137mentioning

confidence: 99%

“…Considered together, these studies suggest that an increase in one of the gaseous mediators can eventually lead to an increase in the other but the picture is obscured by variations across species, pathological models and tissue types. The NO-dependency of H 2 S has recently been studied by Bibli et al (2015) in an in vivo model of myocardial infarction using two species, rabbit and mouse. Pharmacologically limiting NO availability with L-NAME did not limit the protection of NaSH in rabbits, while genetic mutation or pharmacological blockade of eNOS totally abolished H 2 S-induced protection in mice.…”

Section: Dependency Of Gyy4137-postconditioning On Nomentioning

confidence: 99%

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Pharmacological postconditioning against myocardial infarction with a slow-releasing hydrogen sulfide donor, GYY4137

Karwi

Whiteman

Wood

et al. 2016

Pharmacological Research

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Section: Gyy4137 Postconditioning Activates Pi3k/akt Signallingcontrasting

confidence: 44%

Section: Infarct Limitation By Gyy4137mentioning

confidence: 99%

Section: Dependency Of Gyy4137-postconditioning On Nomentioning

confidence: 99%

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Pharmacological postconditioning against myocardial infarction with a slow-releasing hydrogen sulfide donor, GYY4137

Karwi

Whiteman

Wood

et al. 2016

Pharmacological Research

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“…NaHS can additionally enhance cGMP levels by promoting endothelial nitric oxide synthase (eNOS) phosphorylation and increasing nitric oxide (NO) production (Bibli et al, 2015). We and others have observed that the infarct-limiting action of sulfide salts is NO-dependent (King et al, 2014;Bibli et al, 2015;Sun et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Cardioprotection by H2S Donors: Nitric Oxide-Dependent and -Independent Mechanisms

Chatzianastasiou

Bibli²,

Andreadou³

et al. 2016

Journal of Pharmacology and Experimental Therapeutics

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Hydrogen sulfide (H 2 S) is a signaling molecule with protective effects in the cardiovascular system. To harness the therapeutic potential of H 2 S, a number of donors have been developed. The present study compares the cardioprotective actions of representative H 2 S donors from different classes and studies their mechanisms of action in myocardial injury in vitro and in vivo. Exposure of cardiomyocytes to H 2 O 2 led to significant cytotoxicity, which was inhibited by sodium sulfide (Na 2 S), thiovaline (TV), GYY4137[morpholin-4-ium 4 methoxyphenyl(morpholino) phosphinodithioate], and AP39 [(10-oxo-10-(4-(3-thioxo-3H-1,2-dithiol5yl)-phenoxy)decyl) triphenylphospho-nium bromide]. Inhibition of nitric oxide (NO) synthesis prevented the cytoprotective effects of Na 2 S and TV, but not GYY4137 and AP39, against H 2 O 2 -induced cardiomyocyte injury. Mice subjected to left anterior descending coronary ligation were protected from ischemia-reperfusion injury by the H 2 S donors tested. Inhibition of nitric oxide synthase (NOS) in vivo blocked only the beneficial effect of Na 2 S. Moreover, Na 2 S, but not AP39, administration enhanced the phosphorylation of endothelial NOS and vasodilator-associated phosphoprotein. Both Na 2 S and AP39 reduced infarct size in mice lacking cyclophilin-D (CypD), a modulator of the mitochondrial permeability transition pore (PTP). Nevertheless, only AP39 displayed a direct effect on mitochondria by increasing the mitochondrial Ca 21 retention capacity, which is evidence of decreased propensity to undergo permeability transition. We conclude that although all the H 2 S donors we tested limited infarct size, the pathways involved were not conserved. Na 2 S had no direct effects on PTP opening, and its action was nitric oxide dependent. In contrast, the cardioprotection exhibited by AP39 could result from a direct inhibitory effect on PTP acting at a site different than CypD.

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“…The ischemic region (area at risk) was determined as the percentage of red plus white in relation to the total area (red plus white plus blue). Infarct size was determined as the percentage of white compared with the total area of white plus red as previously described 27. The nonischemic, ischemic, and infarct regions were quantified by ImageJ software.…”

Section: Methodsmentioning

confidence: 99%

The neuroprotective agent Rasagiline mesylate attenuates cardiac remodeling after experimental myocardial infarction

Varela¹,

Mavroidis

Katsimpoulas³

et al. 2017

ESC Heart Failure

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AimRasagiline mesylate (N‐propargyl‐1 (R)‐aminoindan) (RG) is a selective, potent irreversible inhibitor of monoamine oxidase‐B with cardioprotective and anti‐apoptotic properties. We investigated whether it could be cardioprotective in a rat model undergoing experimental myocardial infarction (MI) by permanent ligation of the left anterior descending coronary artery.Methods and resultsRG was administered, intraperitoneally, for 28 days (2 mg/kg) starting 24 h after MI induction. Echocardiography analysis revealed a significant reduction in left ventricular end‐systolic and diastolic dimensions and preserved fractional shortening in RG‐treated compared with normal saline group at 28 days post‐MI (31.6 ± 2.3 vs. 19.6 ± 1.8, P < 0.0001), respectively. Treatment with RG prevented tissue fibrosis as indicated by interstitial collagen estimation by immunofluorescence staining and hydroxyproline content and attenuated the number of apoptotic myocytes in the border zone (65%) as indicated by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Caspase 3 relative protein levels were significantly decreased in the non‐infarcted myocardium. Markedly decreased malondialdehyde levels in the border zone indicate a reduction in tissue oxidative stress.ConclusionsOur study demonstrates a positive effect of RG in the post‐MI period with a significant attenuation in cardiac remodelling.

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

Abstract: 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.

Cited by 74 publications

References 64 publications

Pharmacological postconditioning against myocardial infarction with a slow-releasing hydrogen sulfide donor, GYY4137

Pharmacological postconditioning against myocardial infarction with a slow-releasing hydrogen sulfide donor, GYY4137

Cardioprotection by H2S Donors: Nitric Oxide-Dependent and -Independent Mechanisms

The neuroprotective agent Rasagiline mesylate attenuates cardiac remodeling after experimental myocardial infarction

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