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Melatonin protects against thoracic aortic aneurysm and dissection through SIRT1‐dependent regulation of oxidative stress and vascular smooth muscle cell loss
Author(s) -
Xia Lin,
Sun Chang,
Zhu Hanzhao,
Zhai Mengen,
Zhang Liyun,
Jiang Liqing,
Hou Peng,
Li Junfeng,
Li Kaifeng,
Liu Zhenhua,
Li Buying,
Wang Xiaowu,
Yi Wei,
Liang Hongliang,
Jin Zhenxiao,
Yang Jian,
Yi Dinghua,
Liu Jincheng,
Yu Shiqiang,
Duan Weixun
Publication year - 2020
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/jpi.12661
Subject(s) - melatonin , oxidative stress , vascular smooth muscle , endocrinology , receptor , medicine , thoracic aorta , melatonin receptor , elastin , matrix metalloproteinase , thoracic aortic aneurysm , aortic aneurysm , adventitia , aorta , endogeny , biology , chemistry , pathology , smooth muscle
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 β‐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.