肌浆网钙释放通道稳定剂治疗抑制代谢性 HFpEF 新型模型中的钙触发心律失常。
Ryanodine receptor stabilization therapy suppresses Ca- based arrhythmias in a novel model of metabolic HFpEF.
机构信息
Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD, USA; Division of Cardiovascular Medicine, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Center for Biomedical Engineering and Technology, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA; Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA.
出版信息
J Mol Cell Cardiol. 2024 Oct;195:68-72. doi: 10.1016/j.yjmcc.2024.07.006. Epub 2024 Jul 23.
Heart Failure with preserved ejection fraction (HFpEF) has a high rate of sudden cardiac death (SCD) and empirical treatment is ineffective. We developed a novel preclinical model of metabolic HFpEF that presents with stress-induced ventricular tachycardia (VT). Mechanistically, we discovered arrhythmogenic changes in intracellular Ca handling distinct from the changes pathognomonic for heart failure with reduced ejection fraction. We further show that dantrolene, a stabilizer of the ryanodine receptor Ca channel, attenuates HFpEF-associated arrhythmogenic Ca handling in vitro and suppresses stress-induced VT in vivo. We propose ryanodine receptor stabilization as a mechanistic approach to mitigation of malignant VT in metabolic HFpEF.
射血分数保留的心力衰竭（HFpEF）有很高的心脏性猝死（SCD）发生率，经验性治疗效果不佳。我们建立了一个代谢性 HFpEF 的新型临床前模型，其表现为应激诱导的室性心动过速（VT）。从机制上讲，我们发现了细胞内 Ca 处理的致心律失常变化，与射血分数降低的心力衰竭的典型变化不同。我们进一步表明，丹曲林，一种肌浆网 Ca 通道ryanodine 受体稳定剂，可减轻体外 HFpEF 相关的致心律失常 Ca 处理，并抑制体内应激诱导的 VT。我们提出 Ryanodine 受体稳定作为减轻代谢性 HFpEF 恶性 VT 的机制方法。
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