Boneberg Raphael, Pardun Anita, Hannemann Lena, Hildebrandt Olaf, Koehler Ulrich, Kinscherf Ralf, Hildebrandt Wulf
Department of Medical Cell Biology, Institute for Anatomy and Cell Biology, University of Marburg, Robert-Koch-Str. 8, 35032 Marburg, Germany.
Department of Sleep Medicine, Division of Pneumology, Internal Medicine, University Clinics of Marburg, UKGM, Baldingerstr. 43, 35043 Marburg, Germany.
J Clin Med. 2021 Mar 30;10(7):1387. doi: 10.3390/jcm10071387.
Obstructive sleep apnea (OSA) independent of obesity (OBS) imposes severe cardiovascular risk. To what extent plasma cystine concentration (CySS), a novel pro-oxidative vascular risk factor, is increased in OSA with or without OBS is presently unknown. We therefore studied CySS together with the redox state and precursor amino acids of glutathione (GSH) in peripheral blood mononuclear cells (PBMC) in untreated male patients with OSA (apnea-hypopnea-index (AHI) > 15 h, = 28) compared to healthy male controls ( = 25) stratifying for BMI ≥ or < 30 kg m. Fifteen OSA patients were reassessed after 3-5-months CPAP. CySS correlated with cumulative time at an O-saturation <90% (Tu90%) (r = 0.34, < 0.05) beside BMI (r = 0.58, < 0.001) and was higher in subjects with "hypoxic stress" (59.4 ± 2.0 vs. 50.1 ± 2.7 µM, < 0.01) defined as Tu90% ≥ 15.2 min (corresponding to AHI ≥ 15 h). Moreover, CySS significantly correlated with systolic (r = 0.32, < 0.05) and diastolic (r = 0.31, < 0.05) blood pressure. CPAP significantly lowered CySS along with blood pressure at unchanged BMI. Unexpectedly, GSH antioxidant capacity in PBMC was increased with OSA and reversed with CPAP. Plasma CySS levels are increased with OSA-related hypoxic stress and associated with higher blood pressure. CPAP decreases both CySS and blood pressure. The role of CySS in OSA-related vascular endpoints and their prevention by CPAP warrants further studies.
独立于肥胖症（OBS）的阻塞性睡眠呼吸暂停（OSA）会带来严重的心血管风险。目前尚不清楚，作为一种新的促氧化血管危险因素，血浆胱氨酸浓度（CySS）在伴有或不伴有OBS的OSA患者中升高的程度如何。因此，我们研究了未经治疗的男性OSA患者（呼吸暂停低通气指数（AHI）>15次/小时，n = 28）外周血单个核细胞（PBMC）中的CySS以及谷胱甘肽（GSH）的氧化还原状态和前体氨基酸，将其与健康男性对照组（n = 25）进行比较，并根据BMI≥或<30 kg/m²进行分层。15名OSA患者在接受3 - 5个月的持续气道正压通气（CPAP）治疗后进行了重新评估。CySS与血氧饱和度<90%（Tu90%）时的累计时间相关（r = 0.34，P < 0.05），此外还与BMI相关（r = 0.58，P < 0.001），并且在定义为Tu90%≥15.2分钟（对应AHI≥15次/小时）的“低氧应激”受试者中更高（59.4±2.0对50.1±2.7 μM，P < 0.01）。此外，CySS与收缩压（r = 0.32，P < 0.05）和舒张压（r = 0.31，P < 0.05）显著相关。在BMI不变的情况下，CPAP显著降低了CySS以及血压。出乎意料的是，OSA患者PBMC中的GSH抗氧化能力增加，而CPAP治疗后则逆转。血浆CySS水平随OSA相关的低氧应激而升高，并与较高的血压相关。CPAP可降低CySS和血压。CySS在OSA相关血管终点事件中的作用以及CPAP对其的预防作用值得进一步研究。
