Intermittent Hypoxia Alleviates β-Aminopropionitrile Monofumarate Induced Thoracic Aortic Dissection in C57BL/6 Mice
| Autor: | Yongxiang Wei, Yanwen Qin, Xiaolu Jiao, Song Yang, Linyi Li, Juan Li, Yunyun Yang, Jie Du, Lixin Jia, Yueli Wang, Xiao-ping Zhang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Male
medicine.medical_specialty Vascular smooth muscle Aorta Thoracic Lysyl oxidase 030204 cardiovascular system & hematology 030230 surgery Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals Humans Hypoxia Ischemic Postconditioning Cathepsin S Aortic Aneurysm Thoracic biology business.industry Interleukin Intermittent hypoxia Aminopropionitrile Extracellular Matrix Mice Inbred C57BL Aortic Dissection Disease Models Animal Endocrinology chemistry Apoptosis biology.protein Surgery Cardiology and Cardiovascular Medicine business Elastin |
| Zdroj: | European Journal of Vascular and Endovascular Surgery. 59:1000-1010 |
| ISSN: | 1078-5884 |
| Popis: | Objectives Thoracic aortic dissection (TAD) has a high mortality rate. Intermittent hypoxia (IH) triggers both harmful and beneficial effects in numerous physiological systems. The effects of IH on TAD development were explored in a mouse model. Methods β-Aminopropionitrile monofumarate (BAPN) was used to induce TAD in C57BL/6 mice. Three week old male mice were treated with 1 g/kg/day BAPN in drinking water for four weeks and simultaneously subjected to IH (n = 30) (21%–5% O2, 90 s/cycle, 10 h/day, IH + BAPN group) or normoxia (n = 30) (21% O2, 24 h/day, BAPN group). Human VSMCs (HUASMCs) exposed to IH (30 min, 5% O2)/re-oxygenation (30 min, 21% O2) cycles with a maximum of 60 min/cycle to detect the effect of IH on HIF-1α and LOX via HIF-1α-siRNA. Results It was found that BAPN administration significantly increased the lumen size and wall thickness of aortas compared with the normal group, but was significantly reversed by IH exposure. Additionally, IH exposure significantly increased the survival rate of BAPN induced TAD (70% vs. 40%). Furthermore, IH exposure reduced BAPN induced elastin breaks and apoptosis of vascular smooth muscle cells. IH exposure also reversed BAPN induced upregulation of inflammation and extracellular matrix (ECM) degradation. Real time polymerase chain reaction (RT-PCR) confirmed that IH inhibited inflammation and ECM degradation related genes interleukin (IL)-1β, IL-6, cathepsin S (Cat S), and matrix metalloproteinase 9 (MMP-9), but upregulated the ECM synthesis related genes lysyl oxidase (LOX) and collagen type I alpha2 (Col1a2) compared with the BAPN group. In vitro results suggest that IH promotes the expression of LOX via HIF-1α. Conclusions The results suggest that IH alleviates BAPN induced TAD in C57BL/6 mice. |
| Databáze: | OpenAIRE |
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