Effect of age on the cardiovascular remodelling induced by chronic intermittent hypoxia as a murine model of sleep apnoea

Abstract

Background and objective Chronic intermittent hypoxia (CIH) is a major determinant of the cardiovascular morbidity associated with obstructive sleep apnoea (OSA), and the magnitude of CIH impact may be influenced by ageing. Here, we assessed the role of ageing in the early cardiovascular structural remodelling induced by severe CIH in a murine model of OSA. Methods Cardiovascular remodelling was assessed in young (2 months old, n = 20) and aged (18 months old, n = 20) C57BL/6 female mice exposed to CIH (20% O2 for 40 s, 5% O2 for 20 s) or normoxia (room air) for 8 weeks (6 h/day). Results Early vascular remodelling was observed in young mice exposed to CIH as illustrated by intima‐media thickening (mean change: 4.6 ± 2.6 μm; P = 0.02), elastin fibre disorganization (mean change: 9.2 ± 4.5%; P = 0.02) and fragmentation (mean change: 2.5 ± 0.8%; P = 0.03), and collagen (mean change: 3.2 ± 0.6%; P = 0.001) and mucopolysaccharide accumulation (mean change: 2.4 ± 0.8%; P = 0.01). In contrast, vascular remodelling was not apparent in aged mice exposed to CIH. Furthermore, left ventricular perivascular fibrosis (mean change: 0.71 ± 0.1; P < 0.001) and hypertrophy (mean change: 0.17 ± 0.1; P = 0.038) were increased by CIH exposure in young mice, but not in aged mice. Principal component analysis identified similar cardiovascular alterations among the young mice exposed to CIH and both older mouse groups, suggesting that CIH induces premature cardiovascular senescence. Conclusion Cardiovascular remodelling induced by severe CIH is affected by the age at which CIH onset occurs, suggesting that the deleterious cardiovascular effects associated with CIH may be more pronounced in younger populations, and such changes resemble chronological age‐related declines in cardiovascular structural integrity.

Proteomic profiling for prediction of recurrent cardiovascular event in patients with acute coronary syndrome and obstructive sleep apnea: A post-hoc analysis from the ISAACC study

“…Clinical and experimental evidence suggests that OSA consequences promote CVDs through specific intermediate mechanisms, such as inflammation, endothelial dysfunction, hypercoagulability, oxidative stress and metabolic dysfunction [25,26]. From animal model studies it has been also postulated that exposure to intermittent hypoxia promotes cardiovascular remodeling that is reversed after normoxia restoration [27]. This finding suggests that remodeling induced by severe chronic intermittent hypoxia is affected by the age at which chronic intermittent hypoxia onset occurs, suggesting that the deleterious cardiovascular effects associated with chronic intermittent hypoxia may be more pronounced in younger populations [27].…”

“…From animal model studies it has been also postulated that exposure to intermittent hypoxia promotes cardiovascular remodeling that is reversed after normoxia restoration [27]. This finding suggests that remodeling induced by severe chronic intermittent hypoxia is affected by the age at which chronic intermittent hypoxia onset occurs, suggesting that the deleterious cardiovascular effects associated with chronic intermittent hypoxia may be more pronounced in younger populations [27]. Although the mechanisms by which OSA promotes cardiovascular disease have been extensively studied and described, few studies have explored whether the manifestation of these mechanisms occurs homogeneously in all patients with OSA.…”

Essential Genes and MiRNA–mRNA Network Contributing to the Pathogenesis of Idiopathic Pulmonary Arterial Hypertension

“…Two groups were provided with food and water ad libitum . At the end of the experiment, we used isoflurane to anesthetize the mice and measured their right ventricular systolic pressure (RVSP) by using a Millar pressure transducer catheter through right-sided heart catheterization, as we previously described ( 13 ). To evaluate the RV remodeling, we weighed the wall of the RV and the left ventricle plus septum (LV+S) to calculate the ratio of (RV/LV+S).…”

Cardiovascular morbidities of obstructive sleep apnea and the role of circulating extracellular vesicles

“…Short-term intermittent hypoxia during sleep that mimics OSA leads to structural alterations in the vasculature that appear to be reversible. 140 In contrast, longterm exposures to similar models of OSA are associated with either partial or minimal function and structural recovery. [141][142][143] Over the last a few years, the role of EVs has changed from being only a marker of vascular integrity toward being a functionally relevant effector in the context of intercellular vascular signaling.…”