Abstract 3004: Intermittent Hypoxia Decreases Aortic Stiffness And Facilitates Abdominal Aortic Aneurysm

Abstract

Introduction: Intermittent hypoxia (IH) is a phenomenon observed with obstructive sleep apnea (OSA), which is highly prevalent in patients with abdominal aortic aneurysm (AAA). However, it remains unknown if IH is a risk factor for the development of AAA. The goal of this study was to determine the effects of IH exposure on arterial stiffness, and to assess whether IH increases the susceptibility to angiotensin (Ang) II-induced AAA in mice. Methods: Male C57BL/6 mice (8-week-old) were subjected to IH (6.5%-21% O 2 , 90 s/cycle, 12 h/day) or room air (RA, 21% O 2 , 24 h/day) for short-term (6 weeks) or long-term (6 months) (n = 10/group). Short-term mice were examined for arterial stiffness by pulse wave velocity (PWV) and atomic force microscopy, while long-term mice were used for AAA studies. To induce AAA, mice were infused with Ang II (1 μg/kg/min) using osmotic minipumps during final 14 days of IH or RA exposure. Sham surgery was performed in control mice. Outcomes were assessed via transabdominal ultrasound imaging and histology. Results: Short-term IH exposure decreased the stiffness of the abdominal (0.88 vs. 2.32 m/s in RA; p=0.0006 ) and thoracic (2.0 vs. 3.5 kPa in RA; p=0.01 ) aorta. Ang II increased abdominal aortic diameter in RA mice compared to sham and long-term IH with Ang II further augmented the aortic diameter (1.56 vs. 1.34 mm in RA Ang II; p=0.03 ) and incidence of AAA (50 vs. 10% in RA Ang II; p=0.05 ). Histologically, long-term IH plus Ang II augmented medial elastin fragmentation (7.7 vs. 5.3 in RA Ang II; p=0.04 ) and aortic collagen content (3.1 vs. 1.3 in RA Ang II; p=0.06 ). Ang II tended to non-significantly increase PWV in both groups (RA sham 1.9 vs. RA Ang II 2.5 and IH Ang II 2.3 m/s). Notably, a negative correlation between maximum aortic diameter and PWV was observed in AAA-induced mice (R 2 =0.48, p=0.0009 ). Conclusions: IH favors AAA development in association with changes in aortic stiffness. These findings support a potential causal link between OSA and AAA pathogenesis. Clarification of the molecular mechanisms may reveal novel therapeutic targets for the management of AAA.