Effect of age on the cardiovascular remodelling induced by chronic intermittent hypoxia as a murine model of sleep apnoea
Effect of age on the cardiovascular remodelling induced by chronic intermittent hypoxia as a murine model of sleep apnoea
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DOI：
10.1111/resp.13610
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发表时间：
2020-03-01
期刊：
影响因子：
6.9
通讯作者：
Sanchez-De-La-Torre, Manuel
中科院分区：
文献类型：
--
作者：
Castro-Grattoni, Anabel L.;Suarez-Giron, Monique;Sanchez-De-La-Torre, Manuel
背景与目的慢性间歇性低氧(CIH)是阻塞性睡眠呼吸暂停(OSA)相关心血管并发症的主要决定因素，其影响的大小可能受年龄的影响。方法对青年(2个月龄，n=20)和老年(18个月龄，n=20)C57BL/6雌性小鼠分别暴露于脑出血(20%O-2，40只S，5%O-2，20只S)和常氧(6h/d)处理8周(6h/d)，观察衰老在严重脑出血所致OSA早期心血管结构重建中的作用。胶原(平均变化：3.2+/-0.6%；P=0.001)和粘多糖堆积(平均变化：2.4+/-0.8%；P=0.01)。相比之下，暴露于CIH的老年小鼠血管重构并不明显。此外，青年组小鼠左室血管周围纤维化(平均变化：0.71+/-0.1；P<；0.001)和肥厚(平均变化：0.17+/-0.1；P=0.038)均增加，但老年小鼠无明显变化。主成分分析发现，暴露于脑出血的年轻小鼠和两个老年小鼠组的心血管改变相似，提示脑出血可导致心血管早衰。结论重度脑出血所致的心血管重构受发病年龄的影响，提示脑出血对心血管的有害影响可能在较年轻的人群中更为明显，这种变化类似于心血管结构完整性的随年龄变化的时间相关性下降。
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% O-2 for 40 s, 5% O-2 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 mu m; 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.