Abstract 12766: Sleep Disruption Promotes Atherosclerosis and Formation of Abdominal Aortic Aneurysms in Mice
Sleep disruption and deprivation, occurring in patients with sleep disorders or in shift workers, are associated with a high incidence of cardiovascular diseases, including atherosclerosis. Recently, a clinical study indicated a link between obstructive sleep apnea and the accelerated progression of abdominal aortic aneurysms (AAA). However, the causative link between sleep disruption and AAA formation is still unknown. Given the fact that sleep disorders are linked to endothelial dysfunction, oxidative stress and atherogenesis (all of which play an important role in pathogenesis of AAA), we tested the hypothesis that sleep disruption is associated with the increased AAA formation. Male ApoE -/-mice were housed in sleep- fragmentation (SF) cages or non-sleep-fragmentation (NSF) cages for 12 weeks. Mice were either fed a high-fat (HF) or normal-chow (NC) diet. After each treatment, aortic tissues and monocytes were collected and monocytes activation, cellular inflammation markers, expression and activity of matrix metalloproteinases (MMPs), atherosclerotic lesion formation and AAA formation were assessed. SF induced AAA formation in 83% of HF ApoE-/- mice, but not in the (NSF) of HF ApoE-/- mice control group. Atherosclerotic lesion formation, as assessed by Oil red O staining at the ascending aorta, was significantly increased in the SF group when compared to the NSF group. SF was associated with monocytes/macrophages activation, increased cellular and plasma inflammation markers and elevated MMP9 expression in monocytes. Furthermore, disruption of aortic intima and media and breaking of elastic lamina were observed in the AAA lesions. Although MMPs is highly expressed in aortas, MMP2 and MMP9 were differentially expressed in the thoracic and abdominal aortas. The expression and activity of MMP2 were significantly increased in the adnominal aorta after the 12 week treatment of SF. In addition, SF also increased macrophage infiltration as evidenced by robust staining of macrophage markers in the AAA lesions. The MMPs staining was co-localized with macrophage markers. Sleep disruption promotes AAA formation through monocyte/macrophage-mediated MMPs expression and subsequent extracellular matrix remodeling in the abdominal aortas.
- © 2012 by American Heart Association, Inc.