Abstract：
The atrophic myocardium resulting from mechanical unloading and nutritional deprivation is considered crucial as maladaptive remodeling directly associated with heart failure, as well as interstitial fibrosis. Conversely, myocardial hypertrophy resulting from hemodynamic loading is perceived as compensatory stress adaptation. We previously reported the abundant presence of highly redox-active polysulfide molecules, termed supersulfide, with two or more sulfur atoms catenated in normal hearts, and the supersulfide catabolism in pathologic hearts after myocardial infarction correlated with worsened prognosis of heart failure. However, the impact of supersulfide on myocardial remodeling remains unclear. Here, we investigated the involvement of supersulfide metabolism in cardiomyocyte remodeling, using a model of adenosine 5\'-triphosphate (ATP) receptor-stimulated atrophy and endothelin-1 receptor-stimulated hypertrophy in neonatal rat cardiomyocytes. Results revealed contrasting changes in intracellular supersulfide and its catabolite, hydrogen sulfide (H2S), between cardiomyocyte atrophy and hypertrophy. Stimulation of cardiomyocytes with ATP decreased supersulfide activity, while H2S accumulation itself did not affect cardiomyocyte atrophy. This supersulfide catabolism was also involved in myofibroblast formation of neonatal rat cardiac fibroblasts. Thus, unraveling supersulfide metabolism during myocardial remodeling may lead to the development of novel therapeutic strategies to improve heart failure.
摘要：
机械卸载和营养剥夺导致的萎缩性心肌被认为是与心力衰竭直接相关的适应不良重塑的关键。以及间质纤维化。相反，由血流动力学负荷引起的心肌肥大被认为是代偿性应激适应。我们以前报道了大量存在高氧化还原活性的多硫化物分子，称为超硫化物，两个或多个硫原子连接在正常心脏中，心肌梗死后病理性心脏中超硫化物分解代谢与心力衰竭预后恶化相关。然而,超硫化物对心肌重塑的影响尚不清楚.这里,我们研究了超硫化物代谢在心肌细胞重塑中的参与，使用新生大鼠心肌细胞中腺苷5'-三磷酸（ATP）受体刺激的萎缩和内皮素-1受体刺激的肥大模型。结果揭示了细胞内超硫化物及其分解代谢物的对比变化，硫化氢(H2S),心肌细胞萎缩和肥大之间。用ATP刺激心肌细胞的超硫化物活性降低，而H2S积累本身并不影响心肌细胞萎缩。这种超硫化物分解代谢也参与新生大鼠心脏成纤维细胞的肌成纤维细胞形成。因此，心肌重塑过程中超硫化物代谢的瓦解可能导致新的治疗策略的发展，以改善心力衰竭。
