(715.26) Intermittent Hypoxia Promotes the Development of Abdominal Aortic Aneurysm in Male Mice
Monday, April 4, 2022
10:15 AM – 12:15 PM
Location: Exhibit/Poster Hall A-B - Pennsylvania Convention Center
Poster Board Number: E103
Neekun Sharma (University of Missouri), Gavin Power (University of Missouri), Rogerio Soares (University of Missouri), Francisco Ramirez-Perez (University of Missouri), Abdelnaby Khalyfa (University of Missouri), David Gozal (University of Missouri), Luis Martinez-Lemus (University of Missouri), Camila Manrique-Acevedo (University of Missouri), Jaume Padilla (University of Missouri)
Introduction. Intermittent hypoxia (IH) is one of the hallmarks of obstructive sleep apnea (OSA). OSA is highly prevalent among patients with abdominal aortic aneurysm (AAA). However, it remains unknown whether IH is a risk factor for the development and faster expansion of AAA. The goal of this study was to determine whether exposure to chronic IH mimicking OSA increases the susceptibility to angiotensin (Ang) II-induced AAA in mice.
Methods. Four- to six-week-old male C57BL/6 mice (n = 20/group) were subjected to IH (6.5%-21% O2, 90 s/cycle, 12 h/day during daylight) or room air (21% O2, 24 h/day) for 6 months. During the final 14 days of IH or room air (RA) exposures, 10 mice from each group were infused with Ang II (1000 ng/kg/minute) using a subcutaneously implanted osmotic minipump to induce AAA. Sham surgery was performed in control mice (n = 10/group). Outcome was assessed by transabdominal ultrasound imaging of the abdominal aorta using a Vevo 2100 imaging system followed by histopathological examination.
Results. Ultrasound imaging revealed increased abdominal aortic diameter in RA mice following Ang II infusion compared to sham mice. Exposure to IH significantly augmented the Ang II-induced increase in aortic diameter and incidence of AAA compared to RA Ang II mice. Histologically, IH along with Ang II infusion augmented medial elastin depletion and accumulation of collagen in the aorta. Additionally, IH was also associated with the pathological process of extensive matrix degradation as evidenced by increased matrix metalloproteinase (MMP9) and a disintegrin and metalloproteinase (Adam)17 expression in the aorta following Ang II infusion.
Conclusions. IH exposures simulating OSA promote the development of AAA. Clarification of the underlying molecular mechanisms may reveal novel therapeutic targets for the management of AAA.
