β-Sitosterol attenuates obstructive sleep apnea-related myocardial injury via MALAT1-mediated HIF-1α regulation
Year: 2025
Type: article
Abstract: 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.
Source: Frontiers in Pharmacology
Institution: Fujian University of Traditional Chinese Medicine
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,801
Award: G6171121895
OpenAlex ID: W4415213336