ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1692758
β-Sitosterol attenuates obstructive sleep apnea-related myocardial injury via MALAT1-mediated HIF-1α regulation
Provisionally accepted
- Fujian University of Traditional Chinese Medicine, Fuzhou, China
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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.
Keywords: β-Sitosterol, obstructive sleep apnea, Myocardial injury, MALAT1, HIF-1α, chronic intermittent hypoxia
Received: 26 Aug 2025; Accepted: 03 Oct 2025.
Copyright: © 2025 Wu, Chen, Li, Liu, Wang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Qin Chen, 2014015@fjtcm.edu.cn
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