ArticleBasic research in cardiology2015
Inhibition of mammalian target of rapamycin protects against reperfusion injury in diabetic heart through STAT3 signaling.
Article in Basic research in cardiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 71 citations in OpenAlex.
- Network Pharmacology & Validation of Dihydrotanshinone I's Regulation of HIF-1α via STAT3 in Cardiomyocytes.Acta Cardiologica Sinica · 2026Article
- Macrophages lacking TSC2 have mTORC1-dependent increased GPNMB and ameliorate ventricular dysfunction/remodeling after ischemia-reperfusion.Scientific reports · 2025Article
- The Pleiotropic Role of the MicroRNA-17-92 Cluster in Cardiovascular Diseases and Cancer.Reviews in cardiovascular medicine · 2025Review
- Mechanisms and Therapeutic Strategies for Myocardial Ischemia-Reperfusion Injury in Diabetic States.ACS pharmacology & translational science · 2024Review
- Intermedin Alleviates Diabetic Cardiomyopathy by Up-Regulating CPT-1β through Activation of the Phosphatidyl Inositol 3 Kinase/Protein Kinase B Signaling Pathway.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Article
- Role and molecular mechanisms of SGLT2 inhibitors in pathological cardiac remodeling (Review).Molecular medicine reports · 2024Review
- High-density lipoprotein protects normotensive and hypertensive rats against ischemia-reperfusion injury through differential regulation of mTORC1 and mTORC2 signaling.Frontiers in pharmacology · 2024Article
- Brazil nut (Food & nutrition research · 2024Article
- Article
- mTOR Signaling: New Insights into Cancer, Cardiovascular Diseases, Diabetes and Aging.International journal of molecular sciences · 2023Article
- Single-Dose Treatment with Rapamycin Preserves Post-Ischemic Cardiac Function through Attenuation of Fibrosis and Inflammation in Diabetic Rabbit.International journal of molecular sciences · 2023Article
- Adenosine 2 receptor regulates autophagy and apoptosis to alleviate ischemia reperfusion injury in type 2 diabetes via IRE-1 signaling.BMC cardiovascular disorders · 2023Article
- Cardioprotective Effects of 1-(3,6-Dibromo-carbazol-9-yl)-3-Phenylamino-Propan-2-Ol in Diabetic Hearts via Nicotinamide Phosphoribosyltransferase Activation.The Journal of pharmacology and experimental therapeutics · 2022Article
- Preclinical model of type 1 diabetes and myocardial ischemia/reperfusion injury in conscious rabbits-demonstration of cardioprotection with rapamycin.STAR protocols · 2021Article
- The role of G protein-coupled receptor kinase 4 in cardiomyocyte injury after myocardial infarction.European heart journal · 2021Article
- Remote liver ischemic preconditioning attenuates myocardial ischemia/reperfusion injury in streptozotocin-induced diabetic rats.Scientific reports · 2021Article
- Potential Mechanisms of Triptolide against Diabetic Cardiomyopathy Based on Network Pharmacology Analysis and Molecular Docking.Journal of diabetes research · 2021Article
- Differential Regulation of mTOR Complexes with miR-302a Attenuates Myocardial Reperfusion Injury in Diabetes.iScience · 2020Article
- STAT3-miR-17/20 signalling axis plays a critical role in attenuating myocardial infarction following rapamycin treatment in diabetic mice.Cardiovascular research · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Diabetic patients suffer augmented severity of myocardial infarction. Excessive activation of the mammalian target of rapamycin (mTOR) and decreased activation of STAT3 are implicated in diabetic complications. Considering the potent cardioprotective effect of mTOR inhibitor, rapamycin, we hypothesized that reperfusion therapy with rapamycin would reduce infarct size in the diabetic hearts through STAT3 signaling. Hearts from adult male db/db or wild type (WT) C57 mice were isolated and subjected to 30 min of normothermic global ischemia and 60 min of reperfusion in Langendorff mode. Rapamycin (100 nM) was infused at the onset of reperfusion. Myocardial infarct size (IS) was significantly reduced in rapamycin-treated mice (13.3 ± 2.4 %) compared to DMSO vehicle control (35.9 ± 0.9 %) or WT mice (27.7 ± 1.1 %). Rapamycin treatment restored phosphorylation of STAT3 and enhanced AKT phosphorylation (target of mTORC2), but significantly reduced ribosomal protein S6 phosphorylation (target of mTORC1) in the diabetic heart. To determine the cause and effect relationship of STAT3 in cardioprotection, inducible cardiac-specific STAT3-deficient (MCM TG:STAT3(flox/flox)) and WT mice (MCM TG:STAT3(flox/flox)) were made diabetic by feeding high fat diet (HFD). Rapamycin given at reperfusion reduced IS in WT mice but not in STAT3-deficient mice following I/R. Moreover, cardiomyocytes isolated from HFD-fed WT mice showed resistance against necrosis (trypan blue staining) and apoptosis (TUNEL assay) when treated with rapamycin during reoxygenation following simulated ischemia. Such protection was absent in cardiomyocytes from HFD-fed STAT3-deficient mice. STAT3 signaling plays critical role in reducing IS and attenuates cardiomyocyte death following reperfusion therapy with rapamycin in diabetic heart.
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