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恩格列净可减轻人诱导多能干细胞衍生心肌细胞中高糖诱导的心肌病:人诱导多能干细胞衍生心肌细胞中的葡萄糖诱导脂毒性。

Empagliflozin Reduces High Glucose-Induced Cardiomyopathy in hiPSC-Derived Cardiomyocytes : Glucose-induced Lipotoxicity in hiPSC-Derived Cardiomyocytes.

作者信息

Tsai Hsiu-Hui, Hsiao Fu-Chih, Yu Alice L, Juang Jyuhn-Huarng, Yu John, Chu Pao-Hsien

机构信息

Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.

Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.

出版信息

Stem Cell Rev Rep. 2025 Apr;21(3):849-858. doi: 10.1007/s12015-024-10839-8. Epub 2025 Jan 22.

DOI:10.1007/s12015-024-10839-8
PMID:39841369
Abstract

Human-induced pluripotent stem cell (hiPSC) technology has been applied in pathogenesis studies, drug screening, tissue engineering, and stem cell therapy, and patient-specific hiPSC-derived cardiomyocytes (hiPSC-CMs) have shown promise in disease modeling, including diabetic cardiomyopathy. High glucose (HG) treatment induces lipotoxicity in hiPSC-CMs, as evidenced by changes in cell size, beating rate, calcium handling, and lipid accumulation. Empagliflozin, an SGLT2 inhibitor, effectively mitigates the hypertrophic changes, abnormal calcium handling, and contractility impairment induced by HG. Glucose concentration influences SGLT2 expression in cardiomyocytes, highlighting its potential role in diabetic cardiomyopathy. These findings support the potential utility of hiPSC-CMs in studying diabetic cardiomyopathy and the efficacy of empagliflozin in ameliorating HG-induced cardiomyocyte dysfunction. Such research may advance developments in precision medicine and therapeutic interventions for patients with diabetic cardiomyopathy.

摘要

人诱导多能干细胞(hiPSC)技术已应用于发病机制研究、药物筛选、组织工程和干细胞治疗,且患者特异性的hiPSC衍生心肌细胞(hiPSC-CMs)在包括糖尿病性心肌病在内的疾病建模中显示出前景。高糖(HG)处理会在hiPSC-CMs中诱导脂毒性,细胞大小、搏动率、钙处理和脂质积累的变化证明了这一点。恩格列净,一种SGLT2抑制剂,可有效减轻HG诱导的肥大变化、异常钙处理和收缩功能障碍。葡萄糖浓度会影响心肌细胞中SGLT2的表达,突出了其在糖尿病性心肌病中的潜在作用。这些发现支持了hiPSC-CMs在研究糖尿病性心肌病中的潜在效用以及恩格列净改善HG诱导的心肌细胞功能障碍的疗效。此类研究可能会推动糖尿病性心肌病患者精准医学和治疗干预的发展。

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Empagliflozin Reduces High Glucose-Induced Cardiomyopathy in hiPSC-Derived Cardiomyocytes : Glucose-induced Lipotoxicity in hiPSC-Derived Cardiomyocytes.恩格列净可减轻人诱导多能干细胞衍生心肌细胞中高糖诱导的心肌病:人诱导多能干细胞衍生心肌细胞中的葡萄糖诱导脂毒性。
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本文引用的文献

1
Diabetic cardiomyopathy: Early diagnostic biomarkers, pathogenetic mechanisms, and therapeutic interventions.糖尿病性心肌病:早期诊断生物标志物、发病机制及治疗干预措施
Cell Death Discov. 2023 Jul 21;9(1):256. doi: 10.1038/s41420-023-01553-4.
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SGLT2 inhibitor ameliorates endothelial dysfunction associated with the common alcohol flushing variant.钠-葡萄糖协同转运蛋白 2 抑制剂改善常见酒精潮红变异相关的内皮功能障碍。
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Dapagliflozin across the range of ejection fraction in patients with heart failure: a patient-level, pooled meta-analysis of DAPA-HF and DELIVER.达格列净在射血分数不同的心力衰竭患者中的应用:来自 DAPA-HF 和 DELIVER 研究的患者水平汇总荟萃分析。
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Dapagliflozin in Heart Failure with Mildly Reduced or Preserved Ejection Fraction.达格列净治疗射血分数轻度降低或保留的心力衰竭。
N Engl J Med. 2022 Sep 22;387(12):1089-1098. doi: 10.1056/NEJMoa2206286. Epub 2022 Aug 27.
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KDM3A Inhibition Ameliorates Hyperglycemia-Mediated Myocardial Injury by Epigenetic Modulation of Nuclear Factor Kappa-B/P65.KDM3A抑制通过对核因子κB/P65的表观遗传调控改善高血糖介导的心肌损伤。
Front Cardiovasc Med. 2022 Apr 29;9:870999. doi: 10.3389/fcvm.2022.870999. eCollection 2022.
8
Direct cardiac effects of SGLT2 inhibitors.钠-葡萄糖协同转运蛋白 2 抑制剂的心脏直接作用。
Cardiovasc Diabetol. 2022 Mar 18;21(1):45. doi: 10.1186/s12933-022-01480-1.
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Mechanisms of cardiac dysfunction in diabetic cardiomyopathy: molecular abnormalities and phenotypical variants.糖尿病性心肌病中心脏功能障碍的机制:分子异常与表型变异
Heart Fail Rev. 2023 May;28(3):597-606. doi: 10.1007/s10741-021-10200-y. Epub 2022 Jan 10.
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Effect of empagliflozin in patients with heart failure across the spectrum of left ventricular ejection fraction.恩格列净对射血分数范围广泛的心力衰竭患者的影响。
Eur Heart J. 2022 Feb 3;43(5):416-426. doi: 10.1093/eurheartj/ehab798.