Exploring cuproptosis as a mechanism and potential intervention target in cardiovascular diseases

Abstract

Copper (Cu) is a vital trace element for maintaining human health. Current evidence suggests that genes responsible for regulating copper influx and detoxification help preserve its homeostasis. Adequate Cu levels sustain normal cardiac and blood vessel activity by maintaining mitochondrial function. Cuproptosis, unlike other forms of cell death, is characterized by alterations in mitochondrial enzymes. Therapeutics targeting cuproptosis in cardiovascular diseases (CVDs) mainly include copper chelators, inhibitors of copper chaperone proteins, and copper ionophores. In this review, we expound on the primary mechanisms, critical proteins, and signaling pathways involved in cuproptosis, along with its impact on CVDs and the role it plays in different types of cells. Additionally, we explored the influence of key regulatory proteins and signaling pathways associated with cuproptosis on CVDs and determined whether intervening in copper metabolism and cuproptosis can enhance the outcomes of CVDs. The insights from this review provide a fresh perspective on the pathogenesis of CVDs and new targets for intervention in these diseases.

A novel cuproptosis‐related prognostic gene signature in adrenocortical carcinoma

“…In terms of ongoing or future studies that explore the therapeutic targeting of cuproptosis in ACC, there indeed exist studies that investigate cuproptosis as a mechanism and potential intervention target in various diseases. 31 , 32 , 33 For instance, the use of copper chelators, inhibitors of copper chaperone proteins, and copper ionophores could potentially serve as therapeutics targeting cuproptosis in cardiovascular diseases. 31 Moreover, tetrathiomolybdate (TTM), a copper‐chelating agent known for its high affinity for copper, is currently utilized in the treatment of Wilson's disease, a condition characterized by the excessive accumulation of copper in the liver.…”

“… 31 , 32 , 33 For instance, the use of copper chelators, inhibitors of copper chaperone proteins, and copper ionophores could potentially serve as therapeutics targeting cuproptosis in cardiovascular diseases. 31 Moreover, tetrathiomolybdate (TTM), a copper‐chelating agent known for its high affinity for copper, is currently utilized in the treatment of Wilson's disease, a condition characterized by the excessive accumulation of copper in the liver. 34 However, studies specifically focusing on ACC are currently limited.…”

Research trends in lipid-lowering therapies for coronary heart disease combined with hyperlipidemia: a bibliometric study and visual analysis

“…Recent research has proposed several unconventional treatment methods, such as cuproptosis therapy, endoplasmic reticulum stress inhibition therapy, and therapies involving H 2 S or SO 2 . A study published by Yang et al noted an increased presence of copper ions within atherosclerotic plaques; however, an excessive deficiency of copper ions can elevate cholesterol levels (Yang et al, 2023). These seemingly contradictory findings may be attributed to the impact of copper ions on endothelial inflammatory factors.…”