Abstract 316: Chronic Intermittent Hypoxia Attenuates BAPN Induced Thoracic Aortic Aneurysms in Mice

Abstract

Objective: Aortic aneurysm (AA) is a life-threatening cardiovascular disorder due to the predisposition for dissection and rupture. Chronic intermittent hypoxia (CIH) has protective effects on heart and brain against ischemia injury. However, whether CIH prevents against AA formation was not elucidated. The present study aimed to investigate the effect of CIH treatment on thoracic aortic aneurysms (TAA) in mice. Approach and Results: Seventy-five C57BL/6 mice 3 weeks of age were divided into three groups, i.e. Control group ( 21% O 2 , 24 h per day, 4 weeks, n = 15); β-aminopropionitrile (BAPN) group (oral administration BAPN 1g / kg / day, 21% O 2 , 24 h per day, 4 weeks, n = 30); CIH+BAPN group ( 5% -21% O 2 90s / cycle, 8h per day, 4 weeks; BAPN 1g / kg / day, n = 30). We found that CIH significantly reduced the incidence of TAA (18 of 30 versus 9 of 30; p<0.05), and decreased maximal aortic diameter in BAPN group by hematoxylin and eosin staining (1.71 ± 0.35 versus 1.23± 0.15 mm; p <0.05). CIH significantly reduced elastin breaks in BAPN group by Verhoeff-van Gieson staining. The apoptosis of vascular smooth muscle cells was detected by TUNEL staining increased in BAPN group and markedly reversed by CIH. Moreover, RNA-Seq analysis and bioinformatics analysis were performed to screen the differential expression genes and possible pathway. CIH significantly down-regulated the expression of inflammation signaling pathways, up-regulated the expression of PI3K/AKT survival pathway and extracellular matrix homeostasis related pathway in BAPN induced TAA mice. Confirmed by real-time quantitative reverse-transcription-polymerase chain reaction (qRT-PCR) assays, CIH significantly inhibited the expression of IL-1β, TNF-α, MMP-9 and Cathepsin S, and increased the expression of hypoxia inducible factor-1α (HIF-1α), Lysyl oxidase (LOX), ITGB1 and COL1A2. Our findings also showed that the expression of MMP-9, MMP-2, cathepsin S, IL-1β, MCP-1 and Mac-2 increased in BAPN group and markedly decreased in CIH+BAPN group by immunohistochemistry staining. Besides, CIH also significantly increased the protein expression of HIF-1α, LOX and p-AKT by western blot analysis. Conclusions: The findings from our study suggest that CIH prevented the TAA development of BAPN-induced mice.