Morphological and structural remodeling of the heart, including cardiac hypertrophy and fibrosis, has been considered a therapeutic target for heart failure for approximately three decades. Groundbreaking heart failure medications demonstrating reverse remodeling effects have contributed significantly to medical advancements. However, nearly 50% of heart failure patients still exhibit drug resistance, posing a challenge to the healthcare system. Recently, characteristics of heart failure resistant to ARBs and β-blockers have been defined, highlighting preserved systolic function despite impaired diastolic function, leading to the classification of heart failure with preserved ejection fraction (HFpEF). The pathogenesis and etiology of HFpEF may be related to metabolic abnormalities, as evidenced by its mimicry through endothelial dysfunction and excessive intake of high-fat diets. Our recent findings indicate a significant involvement of mitochondrial hyper-fission in the progression of heart failure. This mitochondrial pathological remodeling is associated with redox imbalance, especially hydrogen sulfide accumulation due to abnormal electron leak in myocardium. In this review, we also introduce a novel therapeutic strategy for heart failure from the current perspective of mitochondrial redox-metabolic remodeling.

中文翻译：

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心脏重塑：新的病理生理机制和治疗策略

大约三十年来，心脏的形态和结构重塑，包括心脏肥大和纤维化，一直被认为是心力衰竭的治疗目标。具有逆重塑作用的突破性心力衰竭药物为医学进步做出了重大贡献。然而，近50%的心力衰竭患者仍然表现出耐药性，给医疗保健系统带来了挑战。最近，对 ARB 和 β 受体阻滞剂耐药的心力衰竭的特征已被定义，强调尽管舒张功能受损但仍保留收缩功能，从而导致射血分数保留心力衰竭 (HFpEF) 的分类。 HFpEF的发病机制和病因可能与代谢异常有关，其通过内皮功能障碍和过量摄入高脂肪饮食所表现出的拟态现象就证明了这一点。我们最近的研究结果表明线粒体过度裂变在心力衰竭的进展中发挥着重要作用。这种线粒体病理性重塑与氧化还原失衡有关，尤其是心肌异常电子泄漏导致的硫化氢积累。在这篇综述中，我们还从当前线粒体氧化还原代谢重塑的角度介绍了一种新的心力衰竭治疗策略。