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

Abstract

Background and Objective: 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.Methods: 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.

Immune patterns of cuproptosis in ischemic heart failure: A transcriptome analysis

“…Copper (Cu) is a vital micronutrient essential for maintaining human physiological homeostasis and influencing pathological processes 10 . Elevated serum copper levels have been observed in patients with HF, suggesting a potential association between copper and HF 11 . However, further validation through fundamental laboratory experiments is required.…”

Comprehensive analysis of cuproptosis-related long non-coding RNAs in prognosis, immune microenvironment infiltration and chemotherapy response of hepatocellular carcinoma

“…[7,8] The content of copper is regulated by a complex network of Cu-dependent proteins, including cuproenzymes, Cu chaperones, and membrane transports, which help maintain copper homeostasis at cellular level. [9] It has been reported that either copper deficiency or accumulation exhibits an association with various diseases, including neurodegenerative diseases, [10–12] cardiovascular disease, [13–16] and cancer. [17–20] Recently, a unique cell death mechanism triggered by copper was discovered and named “cuproptosis.” [21] The process of cuproptosis is closely related to mitochondrial metabolism and the tricarboxylic acid cycle.…”

“…Although the gradual enhancement in treatment strategies have been widely used for HCC treatment, including surgical treatment, immunotherapy, radiotherapy, targeted copper is regulated by a complex network of Cu-dependent proteins, including cuproenzymes, Cu chaperones, and membrane transports, which help maintain copper homeostasis at cellular level. [9] It has been reported that either copper deficiency or accumulation exhibits an association with various diseases, including neurodegenerative diseases, [10][11][12] cardiovascular disease, [13][14][15][16] and cancer. [17][18][19][20] Recently, a unique cell death mechanism triggered by copper was discovered and named "cuproptosis."…”

ZNT1 involves cuproptosis through regulating MTF1-conduced expression of MT1X under copper overload

“…Moreover, exposure to copper may result in copper overload, and the inherent toxicity of copper can lead to biological dysfunction [14]. Copper imbalances, either overload or de ciency, have been associated with many diseases, including anemia, neutropenia, and thrombocytopenia, as well as tumor development and cancer aggressivity [15]. High serum levels of copper have been found in breast, liver and colorectal cancer patients, and mild accumulation of copper in various organs may increase the incidence and progression of cancer [16,17].…”