Sleep medicine · 2025
JWA mediates oxidative stress to promote vascular endothelial repair in obstructive sleep apnea-hypopnea syndrome.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
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Yan Yaru, Lan Jun, Zhang Hongmei, Ren Yi, Cheng Xiu, Li Yanyan, Wu Meng, Lu Junyu
Аннотация
BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSA) can induce various cardiovascular diseases, posing a heavy burden on individuals, families, and society. Current treatments for OSA lack effective drugs, and patient compliance with other invasive treatments is poor. Therefore, this study aimed to explore effective OSA relief medications and delve into their molecular mechanisms.
METHODS: Established rat models of intermittent hypoxia and pulmonary artery endothelial cells (PAECs) models of intermittent hypoxia. Hematoxylin and eosin staining was used to observe pulmonary artery hypertension in rats. Enzyme-linked immunosorbent assay was employed to detect levels of SOD, MDA, IL-6, and TNF-α in rat peripheral blood and PAECs. Western blotting was used to detect changes in Ras homolog gene family member A/Rho-associated coiled-coil forming protein kinase (RhoA/ROCK) signaling and endothelin 1 (ET-1) expression. Reverse transcription quantitative polymerase chain reaction was performed to measure ARF Like GTPase 6 Interacting Protein 5 (ARL6IP5, namely JWA) expression. Transwell assays evaluated migration ability, while cell counting kit-8 assessed proliferation capacity.
RESULTS: In rat models of intermittent hypoxia and PAECs models of intermittent hypoxia, treatment with all-trans retinoic acid (atRA) upregulated JWA expression in a dose-dependent manner. atRA treatment alleviated pulmonary artery wall thickening, oxidative stress, and inflammatory responses induced by intermittent hypoxia in the rat model, promoting endothelial repair. JWA overexpression inhibited the migration and proliferation of PAECs while suppressing oxidative stress responses. Rescue experiments using antioxidant treatment reversed endothelial dysfunction caused by JWA knockdown.
CONCLUSION: atRA upregulates JWA expression, promoting vascular endothelial repair in OSA by inhibiting oxidative stress responses. This suggests the potential of atRA in treating OSA and controlling its progression to pulmonary artery hypertension.
METHODS: Established rat models of intermittent hypoxia and pulmonary artery endothelial cells (PAECs) models of intermittent hypoxia. Hematoxylin and eosin staining was used to observe pulmonary artery hypertension in rats. Enzyme-linked immunosorbent assay was employed to detect levels of SOD, MDA, IL-6, and TNF-α in rat peripheral blood and PAECs. Western blotting was used to detect changes in Ras homolog gene family member A/Rho-associated coiled-coil forming protein kinase (RhoA/ROCK) signaling and endothelin 1 (ET-1) expression. Reverse transcription quantitative polymerase chain reaction was performed to measure ARF Like GTPase 6 Interacting Protein 5 (ARL6IP5, namely JWA) expression. Transwell assays evaluated migration ability, while cell counting kit-8 assessed proliferation capacity.
RESULTS: In rat models of intermittent hypoxia and PAECs models of intermittent hypoxia, treatment with all-trans retinoic acid (atRA) upregulated JWA expression in a dose-dependent manner. atRA treatment alleviated pulmonary artery wall thickening, oxidative stress, and inflammatory responses induced by intermittent hypoxia in the rat model, promoting endothelial repair. JWA overexpression inhibited the migration and proliferation of PAECs while suppressing oxidative stress responses. Rescue experiments using antioxidant treatment reversed endothelial dysfunction caused by JWA knockdown.
CONCLUSION: atRA upregulates JWA expression, promoting vascular endothelial repair in OSA by inhibiting oxidative stress responses. This suggests the potential of atRA in treating OSA and controlling its progression to pulmonary artery hypertension.