Cuproptosis and Cardiovascular Diseases: Mechanisms, Pathophysiology, and Therapeutic Strategies-A Narrative Review.

Abstract

Despite recent efforts and improvements in terms of diagnosis and treatment, cardiovascular diseases (CVDs) remain a prime risk factor for mortality globally; thus, elucidating novel mechanisms underlying the development of these diseases remains essential. There have been significant contributions to identifying the classical means of programmed cell death (PCD), such as apoptosis, necroptosis, pyroptosis, and autophagy, in CVDs. In comparison, although the role of cuproptosis in CVDs is relatively unknown, cuproptosis has recently been revealed as a distinct type of copper-induced cell death with a unique molecular signature and regulation compared to conventional forms of PCD. Thus, cuproptosis represents a novel approach for treating CVDs. To investigate such implications in this review, we will systematically study the cellular mechanisms of cuproptosis and its pathophysiological roles in various forms of CVD. Finally, based on such mechanistic knowledge and to bridge mechanistic research with clinical applications, we propose the use of therapeutic strategies such as copper chelation, antioxidant modalities, and ferredoxin 1 (FDX1)/lipoic acid synthetase (LIAS)-based biomarkers.