期刊
JOURNAL OF PINEAL RESEARCH
卷 69, 期 1, 页码 -出版社
WILEY
DOI: 10.1111/jpi.12661
关键词
melatonin; melatonin receptor; oxidative stress; sirtuin-1; thoracic aortic aneurysm and dissection; vascular smooth muscle cell
资金
- National Key Research and Development Program of China [2016YFC1301900]
- National Natural Science Foundation of China [81870218, 81770373, 81570230, 81970213]
- Science and Technology Research and Development Program of Shaanxi Province [2017ZDXM-SF-051, 2019ZDLSF01-01-02]
Melatonin functions as an endogenous protective molecule in multiple vascular diseases, whereas its effects on thoracic aortic aneurysm and dissection (TAAD) and underlying mechanisms have not been reported. In this study, TAAD mouse model was successfully induced by beta-aminopropionitrile fumarate (BAPN). We found that melatonin treatment remarkably prevented the deterioration of TAAD, evidenced by decreased incidence, ameliorated aneurysmal dilation and vascular stiffness, improved aortic morphology, and inhibited elastin degradation, macrophage infiltration, and matrix metalloproteinase expression. Moreover, melatonin blunted oxidative stress damage and vascular smooth muscle cell (VSMC) loss. Notably, BAPN induced a decrease in SIRT1 expression and activity of mouse aorta, whereas melatonin treatment reversed it. Further mechanistic study demonstrated that blocking SIRT1 signaling partially inhibited these beneficial effects of melatonin on TAAD. Additionally, the melatonin receptor was involved in this phenomenon. Our study is the first to report that melatonin exerts therapeutic effects against TAAD by reducing oxidative stress and VSMC loss via activation of SIRT1 signaling in a receptor-dependent manner, thus suggesting a novel therapeutic strategy for TAAD.
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