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中重度阻塞性睡眠呼吸暂停与端粒延长有关。

Moderate-to-severe obstructive sleep apnea is associated with telomere lengthening.

作者信息

Polonis Katarzyna, Somers Virend K, Becari Christiane, Covassin Naima, Schulte Phillip J, Druliner Brooke R, Johnson Ruth A, Narkiewicz Krzysztof, Boardman Lisa A, Singh Prachi

机构信息

Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota.

Department of Hypertension and Diabetology, Medical University of Gdansk, Gdansk, Poland.

出版信息

Am J Physiol Heart Circ Physiol. 2017 Nov 1;313(5):H1022-H1030. doi: 10.1152/ajpheart.00197.2017. Epub 2017 Aug 19.

Abstract

Obstructive sleep apnea (OSA) is associated with cardiometabolic diseases. Telomere shortening is linked to hypertension, diabetes mellitus, and cardiovascular diseases. Because these conditions are highly prevalent in OSA, we hypothesized that telomere length (TL) would be reduced in OSA patients. We identified 106 OSA and 104 non-OSA subjects who underwent polysomnography evaluation. Quantitative PCR was used to measure telomere length in genomic DNA isolated from peripheral blood samples. The association between OSA and TL was determined using unadjusted and adjusted linear models. There was no difference in TL between the OSA and non-OSA (control) group. However, we observed a J-shaped relationship between TL and OSA severity: the longest TL in moderate-to-severe OSA [4,918 ± 230 (SD) bp] and the shortest TL in mild OSA (4,735 ± 145 bp). Mean TL in moderate-to-severe OSA was significantly longer than in the control group after adjustment for age, sex, body mass index, hypertension, dyslipidemia, and depression (β = 96.0, 95% confidence interval: 15.4-176.6, = 0.020). In conclusion, moderate-to-severe OSA is associated with telomere lengthening. Our findings support the idea that changes in TL are not unidirectional processes, such that telomere shortening occurs with age and disease but may be prolonged in moderate-to-severe OSA. Here, we show that moderate-to-severe obstructive sleep apnea is associated with longer telomeres, independent of age and cardiovascular risk factors, challenging the hypothesis that telomere shortening is a unidirectional process related to age/disease. A better understanding of the mechanisms underlying telomere dynamics may identify targets for therapeutic intervention in cardiovascular aging/other chronic diseases.

摘要

阻塞性睡眠呼吸暂停(OSA)与心脏代谢疾病相关。端粒缩短与高血压、糖尿病和心血管疾病有关。由于这些病症在OSA中非常普遍,我们推测OSA患者的端粒长度(TL)会缩短。我们确定了106名接受多导睡眠图评估的OSA患者和104名非OSA受试者。使用定量PCR测量从外周血样本中分离的基因组DNA中的端粒长度。使用未调整和调整后的线性模型确定OSA与TL之间的关联。OSA组和非OSA(对照)组之间的TL没有差异。然而,我们观察到TL与OSA严重程度之间呈J形关系:中重度OSA的TL最长[4,918±230(标准差)bp],轻度OSA的TL最短(4,735±145 bp)。在调整年龄、性别、体重指数、高血压、血脂异常和抑郁后,中重度OSA的平均TL显著长于对照组(β = 96.0,95%置信区间:15.4 - 176.6,P = 0.020)。总之,中重度OSA与端粒延长有关。我们的研究结果支持这样一种观点,即TL的变化不是单向过程,端粒缩短会随着年龄和疾病发生,但在中重度OSA中可能会延长。在这里,我们表明中重度阻塞性睡眠呼吸暂停与更长的端粒相关,独立于年龄和心血管危险因素,这对端粒缩短是与年龄/疾病相关的单向过程这一假设提出了挑战。更好地理解端粒动态变化的潜在机制可能会确定心血管衰老/其他慢性疾病治疗干预的靶点。

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