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

• Published in: Respirology (Carlton, Vic.) Vic.), 2020-03, Vol.25 (3), p.312-320
• Main Authors: Castro‐Grattoni, Anabel L., Suarez‐Giron, Monique, Benitez, Ivan, Torres, Marta, Almendros, Isaac, Farre, Ramon, Montserrat, Josep M., Dalmases, Mireia, Gozal, David, Sánchez‐de‐la‐Torre, Manuel, Barbe, Ferran, Girón, Cristina, Martinez‐Bardaji, Ana, Alvarez‐Buvé, Roger
• Format: Article
• Language: English
• Subjects: age; ageing; Aging; Animal models; Apnea; cardiovascular; Collagen; Elastin; Fibrosis; Heart; Hypertrophy; Hypoxia; intermittent hypoxia; Morbidity; obstructive sleep apnoea; Rodents; Senescence; Sleep; Sleep apnea; Sleep disorders; Ventricle
• ISSN: 1323-7799; 1440-1843
• DOI: 10.1111/resp.13610

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