Yang Yan, Liang Lu, Pei Wanjuan, Sun Yinhui
School of Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China.
Front Cardiovasc Med. 2025 Jun 26;12:1611449. doi: 10.3389/fcvm.2025.1611449. eCollection 2025.
Copper (Cu) and iron (Fe) are essential trace elements that are involved in normal human metabolic processes. Disruption of their homeostasis contributes to disease pathogenesis through mechanisms such as cuproptosis and ferroptosis. Cuproptosis targets lipoylated proteins to disrupt mitochondrial respiration, whereas ferroptosis is driven by lipid peroxidation. These processes may independently or interactively exacerbate pulmonary hypertension (PH), a condition characterized by progressive pulmonary vascular remodeling, clinical manifestations of dyspnea, right-sided heart failure, and high mortality, via oxidative stress, metabolic reprogramming, and other mechanisms. This review systematically elucidates: (1) the updated molecular mechanisms of cuproptosis/ferroptosis, (2) research evidence for their roles in PH, and (3) synergistic crosstalk in different subtypes of PH progression. We propose that coordination and regulation of the crosstalk network between cuproptosis and ferroptosis may represent a novel therapeutic strategy for pulmonary vascular remodeling.
铜（Cu）和铁（Fe）是人体正常代谢过程中必需的微量元素。它们体内平衡的破坏通过铜死亡和铁死亡等机制导致疾病发病。铜死亡以脂酰化蛋白为靶点，破坏线粒体呼吸，而铁死亡则由脂质过氧化驱动。这些过程可能通过氧化应激、代谢重编程和其他机制独立或相互作用地加重肺动脉高压（PH），这是一种以进行性肺血管重塑、呼吸困难、右心衰竭等临床表现和高死亡率为特征的疾病。本综述系统地阐明了：（1）铜死亡/铁死亡的最新分子机制，（2）它们在肺动脉高压中作用的研究证据，以及（3）在肺动脉高压进展的不同亚型中的协同相互作用。我们提出，铜死亡和铁死亡之间相互作用网络的协调和调节可能代表一种肺血管重塑的新型治疗策略。
