Cuproptosis, the novel therapeutic mechanism for heart failure: a narrative review.

Abstract

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 (FDX1) 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 FDX1 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.