Yuan Hua-Jing, Xue Yi-Tao, Liu Yang
College of Traditional Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China.
Division of Cardiovascular Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Cardiovasc Diagn Ther. 2022 Oct;12(5):681-692. doi: 10.21037/cdt-22-214.
Heart failure (HF) is a global public health problem with high morbidity, readmission, and mortality rates. The central mediators of cardiomyocyte survival and death are mitochondria. Mitochondria are a key therapeutic target for HF and are closely involved in the pathophysiological process of HF. A recent study proposes that cuproptosis, a novel cell death mechanism, is closely related to mitochondrial respiration. Therefore, this study aims to explore the link between cuproptosis and HF, and to find novel therapeutic targets and treatments for HF.
A literature search (up to April 2022) was conducted through PubMed database, and the search range was limited to publications in English. After further literature search and screening, we found that we are currently the first study to explore the association between HF and cuproptosis.
Research has found that mitochondria are a key therapeutic target in HF and are involved in the pathophysiological processes of energy metabolism, oxidative stress, calcium regulation, and cell death in HF. The micronutrient copper is involved in regulating mitochondrial biological processes, and high serum copper levels are significantly associated with HF. Copper overload affects mitochondrial function and exacerbates the development of HF. And cuproptosis induced by copper overload targeting lipoylated tricarboxylic acid cycle proteins, is closely related to mitochondrial respiration. Copper chelators not only treat HF but also partially rescue copper-mediated cell death. Copper binding to lipoylated components may be the reason for the hyperacetylation of mitochondrial proteins in HF. Ferredoxin 1 () may be an upstream regulator of protein lipoylation and is closely related to cuproptosis.
This study demonstrates the important roles of mitochondria and micronutrient copper in HF. Cuproptosis may be involved in the pathophysiological process of HF and is responsible for the hyperacetylation of mitochondrial proteins in HF. Cuproptosis has the potential to be a novel therapeutic mechanism for HF, and may be a key target for cuproptosis-based treatment of HF. This study provides a new research direction for the treatment of HF and new ideas for the development of new drugs.
心力衰竭（HF）是一个全球性的公共卫生问题，具有高发病率、再入院率和死亡率。心肌细胞存活和死亡的核心介质是线粒体。线粒体是HF的关键治疗靶点，并且密切参与HF的病理生理过程。最近一项研究提出，一种新的细胞死亡机制——铜死亡，与线粒体呼吸密切相关。因此，本研究旨在探索铜死亡与HF之间的联系，并寻找HF的新治疗靶点和治疗方法。
通过PubMed数据库进行文献检索（截至2022年4月），检索范围限于英文出版物。经过进一步的文献检索和筛选，我们发现我们目前是第一项探索HF与铜死亡之间关联的研究。
研究发现线粒体是HF的关键治疗靶点，并且参与HF能量代谢、氧化应激、钙调节和细胞死亡的病理生理过程。微量营养素铜参与调节线粒体生物学过程，高血清铜水平与HF显著相关。铜过载影响线粒体功能并加剧HF的发展。并且由铜过载靶向脂酰化三羧酸循环蛋白诱导的铜死亡与线粒体呼吸密切相关。铜螯合剂不仅治疗HF，还部分挽救铜介导的细胞死亡。铜与脂酰化成分的结合可能是HF中线粒体蛋白过度乙酰化的原因。铁氧化还原蛋白1（）可能是蛋白脂酰化的上游调节因子，并且与铜死亡密切相关。
本研究证明了线粒体和微量营养素铜在HF中的重要作用。铜死亡可能参与HF的病理生理过程，并导致HF中线粒体蛋白的过度乙酰化。铜死亡有潜力成为HF的一种新治疗机制，并且可能是基于铜死亡治疗HF的关键靶点。本研究为HF的治疗提供了新的研究方向和新药开发的新思路。
