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Hydrogen sulfide provides cardioprotection against myocardial/ischemia reperfusion injury in the diabetic state through the activation of the RISK pathway.

Lambert JP, Nicholson CK, Amin H, Amin S, Calvert JW - Med Gas Res (2014)

Bottom Line: Na2S therapy significantly decreased myocardial injury in the db/db diabetic mouse, as evidenced by a reduction in infarct size and circulating troponin-I levels.These studies revealed that Na2S therapy activated the Erk1/2 arm of the Reperfusion Injury Salvage Kinase (RISK) pathway.These findings provide important information that myocardial Erk1/2 activation by Na2S therapy following MI/R sets into motion events, which ultimately lead to cardioprotection in the setting of diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, 380 Northyards Boulevard, Suite B, Atlanta, GA 30313 USA.

ABSTRACT

Background: Coronary artery disease remains the principal cause of death in patients with diabetes mellitus. Diabetic mice display exacerbated injury following myocardial ischemia-reperfusion (MI/R) and are resistant to most therapeutic interventions. We have reported that sodium sulfide (Na2S) therapy confers cardioprotection during MI/R in non-diabetic mice. Here we tested the hypothesis that Na2S therapy would limit the extent of myocardial injury following MI/R when administered at the time of reperfusion.

Methods and results: Diabetic mice (db/db, 12 weeks of age) were subjected to transient myocardial ischemia for a period of 30 minutes followed by reperfusion up to 24 hours. Na2S (0.05 to 1 mg/kg) or saline (vehicle) was administered into the left ventricular lumen at the time of reperfusion. Na2S therapy significantly decreased myocardial injury in the db/db diabetic mouse, as evidenced by a reduction in infarct size and circulating troponin-I levels. The reduction in myocardial injury was also associated with a reduction in oxidative stress and a decrease in cleaved caspase-3 expression. In an effort to evaluate the signaling mechanism responsible for the observed cardioprotection, additional groups of mice were sacrificed during early reperfusion. Hearts were excised and processed for Western blot analysis. These studies revealed that Na2S therapy activated the Erk1/2 arm of the Reperfusion Injury Salvage Kinase (RISK) pathway.

Conclusion: These findings provide important information that myocardial Erk1/2 activation by Na2S therapy following MI/R sets into motion events, which ultimately lead to cardioprotection in the setting of diabetes.

No MeSH data available.


Related in: MedlinePlus

Na2S therapy attenuates MI/R injury in an Erk-dependent manner. Myocardial INF/AAR in diabetic mice subjected to 30 minutes of ischemia followed by 4 hours of reperfusion. Mice were administered vehicle, Na2S (0.1 mg/kg), U0126 (0.1 mg/kg), or a combination of U0126 and Na2S at the time of reperfusion. Values are mean ± SEM. *p < 0.05 vs. Vehicle.
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Fig6: Na2S therapy attenuates MI/R injury in an Erk-dependent manner. Myocardial INF/AAR in diabetic mice subjected to 30 minutes of ischemia followed by 4 hours of reperfusion. Mice were administered vehicle, Na2S (0.1 mg/kg), U0126 (0.1 mg/kg), or a combination of U0126 and Na2S at the time of reperfusion. Values are mean ± SEM. *p < 0.05 vs. Vehicle.

Mentions: To see if the activation of Erk1/2 was necessary for Na2S therapy to provide its infarct sparing effects, U0126 was given alone and in combination with Na2S at the time of reperfusion. U0126 administration alone did not cause any further significant increase or decrease in infarct size compared to Vehicle-treated mice (Figure 6). However U0126 abolished the infarct sparing effects of Na2S therapy.Figure 6


Hydrogen sulfide provides cardioprotection against myocardial/ischemia reperfusion injury in the diabetic state through the activation of the RISK pathway.

Lambert JP, Nicholson CK, Amin H, Amin S, Calvert JW - Med Gas Res (2014)

Na2S therapy attenuates MI/R injury in an Erk-dependent manner. Myocardial INF/AAR in diabetic mice subjected to 30 minutes of ischemia followed by 4 hours of reperfusion. Mice were administered vehicle, Na2S (0.1 mg/kg), U0126 (0.1 mg/kg), or a combination of U0126 and Na2S at the time of reperfusion. Values are mean ± SEM. *p < 0.05 vs. Vehicle.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4269946&req=5

Fig6: Na2S therapy attenuates MI/R injury in an Erk-dependent manner. Myocardial INF/AAR in diabetic mice subjected to 30 minutes of ischemia followed by 4 hours of reperfusion. Mice were administered vehicle, Na2S (0.1 mg/kg), U0126 (0.1 mg/kg), or a combination of U0126 and Na2S at the time of reperfusion. Values are mean ± SEM. *p < 0.05 vs. Vehicle.
Mentions: To see if the activation of Erk1/2 was necessary for Na2S therapy to provide its infarct sparing effects, U0126 was given alone and in combination with Na2S at the time of reperfusion. U0126 administration alone did not cause any further significant increase or decrease in infarct size compared to Vehicle-treated mice (Figure 6). However U0126 abolished the infarct sparing effects of Na2S therapy.Figure 6

Bottom Line: Na2S therapy significantly decreased myocardial injury in the db/db diabetic mouse, as evidenced by a reduction in infarct size and circulating troponin-I levels.These studies revealed that Na2S therapy activated the Erk1/2 arm of the Reperfusion Injury Salvage Kinase (RISK) pathway.These findings provide important information that myocardial Erk1/2 activation by Na2S therapy following MI/R sets into motion events, which ultimately lead to cardioprotection in the setting of diabetes.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, 380 Northyards Boulevard, Suite B, Atlanta, GA 30313 USA.

ABSTRACT

Background: Coronary artery disease remains the principal cause of death in patients with diabetes mellitus. Diabetic mice display exacerbated injury following myocardial ischemia-reperfusion (MI/R) and are resistant to most therapeutic interventions. We have reported that sodium sulfide (Na2S) therapy confers cardioprotection during MI/R in non-diabetic mice. Here we tested the hypothesis that Na2S therapy would limit the extent of myocardial injury following MI/R when administered at the time of reperfusion.

Methods and results: Diabetic mice (db/db, 12 weeks of age) were subjected to transient myocardial ischemia for a period of 30 minutes followed by reperfusion up to 24 hours. Na2S (0.05 to 1 mg/kg) or saline (vehicle) was administered into the left ventricular lumen at the time of reperfusion. Na2S therapy significantly decreased myocardial injury in the db/db diabetic mouse, as evidenced by a reduction in infarct size and circulating troponin-I levels. The reduction in myocardial injury was also associated with a reduction in oxidative stress and a decrease in cleaved caspase-3 expression. In an effort to evaluate the signaling mechanism responsible for the observed cardioprotection, additional groups of mice were sacrificed during early reperfusion. Hearts were excised and processed for Western blot analysis. These studies revealed that Na2S therapy activated the Erk1/2 arm of the Reperfusion Injury Salvage Kinase (RISK) pathway.

Conclusion: These findings provide important information that myocardial Erk1/2 activation by Na2S therapy following MI/R sets into motion events, which ultimately lead to cardioprotection in the setting of diabetes.

No MeSH data available.


Related in: MedlinePlus