β-Sitosterol attenuates obstructive sleep apnea-related myocardial injury via MALAT1-mediated HIF-1α regulation.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with chronic intermittent hypoxia (CIH), which contributes to myocardial injury. Although continuous positive airway pressure (CPAP) is the standard therapy, patient compliance remains challenging. β-Sitosterol, a natural phytosterol with anti-apoptotic properties, has shown potential cardioprotective effects, but its role in OSA-related myocardial injury remains unclear. METHODS: A CIH rat model and hypoxic H9c2 cardiomyocytes were used to evaluate the effects of β-sitosterol. Myocardial injury was assessed via heart-to-body weight ratio, histopathology (H&E, Masson, TUNEL staining), and apoptosis markers. Molecular mechanisms involving lncRNA MALAT1 and HIF-1α were investigated using RT-qPCR, Western blot, RNA-FISH, luciferase assays, and gain-of-function experiments. RESULTS: β-Sitosterol treatment significantly reduced myocardial fibrosis, apoptosis, and structural damage in CIH rats in a dose-dependent manner. In vitro, it enhanced cell viability and suppressed apoptosis under hypoxic conditions. Mechanistically, β-sitosterol downregulated MALAT1 and HIF-1α expression. Although MALAT1 and HIF1A co-localized in the cytoplasm, no direct binding was detected. Overexpression of MALAT1 abolished the protective effects of β-sitosterol and reactivated HIF-1α/Bax/caspase-3 signaling. CONCLUSION: β-Sitosterol attenuates CIH-induced myocardial injury by inhibiting the MALAT1/HIF-1α axis, suggesting its potential as a therapeutic agent for OSA patients with limited tolerance to conventional therapies.