Insulin protects cardiomyocytes against reoxygenation-induced hypercontracture by a survival pathway targeting SR Ca2+ storage☆

Abdallah, Yaser; Gkatzoflia, Anna; Gligorievski, Dragan; Kasseckert, Sascha; Euler, Gerhild; Schlüter, Klaus‐Dieter; Schäfer, Matthias; Piper, H. M.; Schäfer, Claudia

doi:10.1016/j.cardiores.2006.02.020

Cited by 61 publications

(27 citation statements)

References 23 publications

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“…This notion is further supported by the observation that preserving SERCA2 activity attenuates ER stress and prevents myocardial ischemic injury. 36 Activation of PPARα in the adult can decrease circulating free fatty acid levels in vivo by promoting fatty acid β-oxidation in peripheral tissues, 37 thereby limiting the delivery of fatty acids to the myocardium. A similar effect on fatty acid supply in the hypertrophied neonatal heart may not be desirable because accelerating fatty acid β-oxidation in the neonatal hypertrophied heart is associated with reduced ischemic injury.…”

Section: Discussionmentioning

confidence: 99%

Activating PPARα Prevents Post–Ischemic Contractile Dysfunction in Hypertrophied Neonatal Hearts

Lam

Zhang

Huqi

et al. 2015

Circulation Research

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Rationale: Post-ischemic contractile dysfunction is a contributor to morbidity and mortality after the surgical correction of congenital heart defects in neonatal patients. Pre-existing hypertrophy in the newborn heart can exacerbate these ischemic injuries, which may partly be due to a decreased energy supply to the heart resulting from low fatty acid β-oxidation rates.Objective: We determined whether stimulating fatty acid β-oxidation with GW7647, a peroxisome proliferatoractivated receptor-α (PPARα) activator, would improve cardiac energy production and post-ischemic functional recovery in neonatal rabbit hearts subjected to volume overload-induced cardiac hypertrophy. Methods and Results:Volume-overload cardiac hypertrophy was produced in 7-day-old rabbits via an aorto-caval shunt, after which, the rabbits were treated with or without GW7647 (3 mg/kg per day) for 14 days. Biventricular working hearts were subjected to 35 minutes of aerobic perfusion, 25 minutes of global no-flow ischemia, and 30 minutes of aerobic reperfusion. GW7647 treatment did not prevent the development of cardiac hypertrophy, but did prevent the decline in left ventricular ejection fraction in vivo. GW7647 treatment increased cardiac fatty acid β-oxidation rates before and after ischemia, which resulted in a significant increase in overall ATP production and an improved in vitro post-ischemic functional recovery. A decrease in post-ischemic proton production and endoplasmic reticulum stress, as well as an activation of sarcoplasmic reticulum calcium ATPase isoform 2 and citrate synthase, was evident in GW7647-treated hearts. Conclusions:

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Section: Discussionmentioning

confidence: 99%

Activating PPARα Prevents Post–Ischemic Contractile Dysfunction in Hypertrophied Neonatal Hearts

Lam

Zhang

Huqi

et al. 2015

Circulation Research

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“…Twenty-five wild-type (WT) and 22 Mas knockout (Mas Ϫ/Ϫ ) on FVB/N genetic background male mice (3 to 6 months old) were obtained from the transgenic animal facilities of the Federal University of Minas Gerais Laboratory of Hypertension. All of the experimental protocols conform to the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by our institution.…”

Section: Animalsmentioning

confidence: 99%

“…Moreover, there has been some evidence in the literature supporting an interplay among eNOS, cGMPdependent protein kinase, and Ca 2ϩ handling in cardiomyocytes. 22 Accordingly, insulin treatment of cardiomyocytes increased phosphorylation and activity of eNOS, leading to augmented phospholamban phosphorylation and consequent SERCA2a activation in reoxygenated cardiomyocytes. In this context, Ang-(1-7)-dependent NO could modulate the activity of multiple Ca 2ϩ handling proteins in the cell.…”

Section: Ang-(1-7)/mas Signaling Pathways In Adult Ventricular Cardiomentioning

confidence: 99%

Molecular Mechanisms Involved in the Angiotensin-(1-7)/Mas Signaling Pathway in Cardiomyocytes

et al. 2008

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Abstract-Recently there has been growing evidence suggesting that beneficial effects of angiotensin-(1-7) ] in the heart are mediated by its receptor Mas. However, the signaling pathways involved in these effects in cardiomyocytes are unknown. Here, we investigated the involvement of the Ang-(1-7)/Mas axis in NO generation and Ca 2ϩ handling in adult ventricular myocytes using a combination of molecular biology, intracellular Ca 2ϩ imaging, and confocal microscopy. Acute Ang-(1-7) treatment (10 nmol/L) leads to NO production and activates endothelial NO synthase and Akt in cardiomyocytes. Ang-(1-7)-dependent NO raise was abolished by pretreatment with A-779 (1 mol/L). To confirm that Ang-(1-7) action is mediated by Mas, we used cardiomyocytes isolated from Mas-deficient mice. In Mas-deficient cardiomyocytes, Ang-(1-7) failed to increase NO levels. Moreover, Mas-ablation was accompanied by significant alterations in the proteins involved in the regulation of endothelial NO synthase activity, indicating that endothelial NO synthase and its binding partners are important effectors of the Mas-mediated pathway in cardiomyocytes. We then investigated the role of the Ang- (1-7)

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“…PKG activation may be another signaling mechanism that limits reperfusion injury . Abdallah et al (2006) have reported the activation of PKG downstream of PI3K/Akt/eNOS/NO as being critical to the protection afforded by insulin at reoxygenation in isolated cardiomyocytes, whereas pharmaco- FIG. 4.…”

mentioning

confidence: 99%

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

Ferdinándy¹,

Schulz²,

Baxter³

2007

Pharmacol Rev

648

615

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Insulin protects cardiomyocytes against reoxygenation-induced hypercontracture by a survival pathway targeting SR Ca2+ storage☆

Cited by 61 publications

References 23 publications

Activating PPARα Prevents Post–Ischemic Contractile Dysfunction in Hypertrophied Neonatal Hearts

Activating PPARα Prevents Post–Ischemic Contractile Dysfunction in Hypertrophied Neonatal Hearts

Molecular Mechanisms Involved in the Angiotensin-(1-7)/Mas Signaling Pathway in Cardiomyocytes

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

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