CDC25A Alleviates Obstructive Sleep Apnea‐Hypopnea Syndrome With Hypertension and Inhibits Ferroptosis

ABSTRACT Obstructive sleep apnea‐hypopnea syndrome (OSAHS) is significantly correlated with hypertension. This investigation aimed to explore the effect of ferroptosis on OSAHS‐hypertension. Ferroptosis‐associated genes were screened based on the GSE205050 dataset and FerrDb database. An OSAHS‐hypertension model was established by exposing Sprague Dawley rats to chronic intermittent hypoxia for 8 weeks, and human umbilical vein endothelial cells (HUVECs) were exposed to intermittent hypoxia in vitro. CDC25A was overexpressed using recombinant adeno‐associated virus in vivo and plasmid transfection in vitro. Ferroptosis markers, oxidative stress indicators, blood pressure, abdominal aortic tissue histopathology, and endothelial cell viability/apoptosis were then assessed. Six ferroptosis‐associated hub genes were identified, including CDC25A, EZH2, PARP1, HELLS, FANCD2, and RRM2, all of which were lowly expressed. In the rat model of OSAHS‐hypertension, overexpression of CDC25A significantly reduced systolic and diastolic blood pressure as well as vascular wall thickness, while increasing α‐SMA expression. Biochemical analyses showed that CDC25A decreased malondialdehyde (MDA) and Fe 2+ levels while increasing glutathione (GSH), superoxide dismutase (SOD), and ferroptosis‐associated proteins (FTH1, SLC7A11, GPX4). CDC25A overexpression in HUVECs ameliorated hypoxia‐induced endothelial dysfunction by inhibiting ferroptosis and apoptosis and promoting cell survival; however, these protective effects were significantly abrogated by co‐treatment with erastin. CDC25A inhibits OSAHS‐hypertension progression and modulates ferroptosis‐related pathways. This study identifies ferroptosis as a potential therapeutic target in OSAHS‐associated hypertension, with CDC25A acting as a key regulatory factor.