1. Melatonin protects against thoracic aortic aneurysm and dissection through SIRT1‐dependent regulation of oxidative stress and vascular smooth muscle cell loss
- Author
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Zhenxiao Jin, Peng Hou, Jincheng Liu, Zhenhua Liu, Jian Yang, Mengen Zhai, Liyun Zhang, Weixun Duan, Hanzhao Zhu, Junfeng Li, Dinghua Yi, Chang Sun, Lin Xia, Shiqiang Yu, Xiaowu Wang, Hongliang Liang, Wei Yi, Kaifeng Li, Liqing Jiang, and Buying Li
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Vascular smooth muscle ,Myocytes, Smooth Muscle ,Cell ,Matrix metalloproteinase ,medicine.disease_cause ,Thoracic aortic aneurysm ,Melatonin receptor ,Muscle, Smooth, Vascular ,Melatonin ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Sirtuin 1 ,Internal medicine ,medicine ,Animals ,Aortic Aneurysm, Thoracic ,biology ,business.industry ,medicine.disease ,Aortic Dissection ,Oxidative Stress ,030104 developmental biology ,medicine.anatomical_structure ,cardiovascular system ,biology.protein ,business ,hormones, hormone substitutes, and hormone antagonists ,030217 neurology & neurosurgery ,Oxidative stress ,medicine.drug - Abstract
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.
- Published
- 2020