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 Fe²⁺ 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.