Intermittent Hypoxia Reduces Aortic Stiffness in Association with Increased Matrix Metalloproteinase Expression in Male Mice

We previously reported that obstructive sleep apnea (OSA), characterized by episodes of intermittent hypoxia (IH), is associated with heightened incidence of abdominal aortic aneurysm (AAA) development in mice subjected to Angiotensin-II infusion for 14 days. AAA is characterized by increased distention of the aortic wall in response to circumferential stress exerted by the arterial intravascular pressure. Its formation is also associated with increased expression of extracellular matrix (ECM) degrading enzymes. This implies that there is a reduction in the capacity of the arterial wall materials to withstand stress in AAA. Therefore, we hypothesized that exposure to IH in mice reduces arterial stiffness in association with significant changes in ECM degrading enzymes and components of the aortic wall. We tested this hypothesis in eight-week-old C57BL/6J male mice exposed to IH or room air (RA, control) for six weeks. IH significantly decreased PWV (pulse wave velocity) of the abdominal aorta as determined by ultrasound imaging as well as aortic stiffness as assessed by atomic force microscopy in thoracic aorta explants. These reductions in aortic stiffness were associated with a diminished presence of collagen and elastin in the aortic wall in conjunction with increased expression of matrix metalloproteinase (MMP)-9, a disintegrin and metalloproteinase (ADAM)-17, and the MMP regulator, Reversion Inducing Cysteine Rich Protein With Kazal Motifs (RECK). No effects of IH were observed in aortic vasoconstriction or vasodilation capacity as assessed via myography in isolated aortas. We conclude that IH reduces the stiffness of the aortic wall in association with the increased expression of MMPs and degradation of ECM components. We further posit that these changes in aortic stiffness and structure eventually facilitate AAA development in people with OSA. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.