AUTHOR=Yang Yan , Liang Lu , Pei Wanjuan , Sun Yinhui 

TITLE=Interaction of ferroptosis and cuproptosis in the perspective of pulmonary hypertension

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 12 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2025.1611449

DOI=10.3389/fcvm.2025.1611449

ISSN=2297-055X

ABSTRACT=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.