Brandão Luiz Eduardo Mateus, Zhang Lei, Grip Anastasia, Hong Mun-Gwan, Kåks Emil, Benfeitas Rui, Sigurdardottir Fjola, Blennow Kaj, Zetterberg Henrik, Espes Daniel, Omland Torbjørn, Khoonsari Payam Emami, Benedict Christian, Cedernaes Jonathan
Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
Biomark Res. 2025 Apr 29;13(1):67. doi: 10.1186/s40364-025-00776-0.
Biomarker profiling from biofluids such as blood are widely measured in clinical research, using for example Olink proteomics panels. One such research focus area is cardiovascular disease (CVD), for which chronic sleep restriction (SR) is a risk factor. However, it remains unclear whether blood levels of commonly measured CVD biomarkers are sensitive to acute dynamic factors such as SR, physical exercise (PEx), and time of day. In this crossover design, 16 normal-weight, healthy men underwent three highly standardized in-lab nights of SR (4.25 h/night) and normal sleep (NS, 8.5 h/night) in randomized order, with 88 CVD blood protein biomarkers quantified using the Olink technology (and selected validation using ELISA) in the morning, evening, and immediately before and repeatedly after 30 min of high-intensity exercise. We found significant time-of-day-dependent changes in several CVD biomarkers. Whereas several proteins were exercise-induced across sleep conditions (such as the canonical exerkines IL- 6 and BDNF), exercise-induced proteomic dynamics differed in response to recurrent SR, compared with following NS. Moreover, SR compared with NS resulted in a biomarker profile previously associated with increased prospective risk of several CVDs across large-scale cohorts (such as higher circulating levels of IL-27 and LGALS9). Our findings highlight how dynamic physiology can modulate CVD biomarker levels. These results also underscore the need to consider sleep duration as a key determinant of cardiovascular health-an emphasis reflected in recent American Heart Association guidelines. Further studies in women, older individuals, and patients with prior CVD, and across different chronotypes and dietary schedules are warranted.
在临床研究中，广泛采用如Olink蛋白质组学检测板等方法对血液等生物流体中的生物标志物进行分析。其中一个研究重点领域是心血管疾病（CVD），慢性睡眠限制（SR）是其风险因素之一。然而，常用的CVD生物标志物的血液水平是否对SR、体育锻炼（PEx）和一天中的时间等急性动态因素敏感，仍不清楚。在这项交叉设计中，16名体重正常的健康男性按随机顺序经历了三个高度标准化的实验室夜间睡眠限制（4.25小时/晚）和正常睡眠（NS，8.5小时/晚），在早晨、晚上、高强度运动前及运动后30分钟反复进行检测，使用Olink技术对88种CVD血液蛋白质生物标志物进行定量分析（并通过酶联免疫吸附测定法进行选定验证）。我们发现几种CVD生物标志物存在显著的昼夜时间依赖性变化。虽然在不同睡眠条件下有几种蛋白质是运动诱导产生的（如典型的运动因子白细胞介素-6和脑源性神经营养因子），但与正常睡眠后相比，反复睡眠限制后运动诱导的蛋白质组动力学有所不同。此外，与正常睡眠相比，睡眠限制导致了一种生物标志物谱，该谱先前与大规模队列中几种心血管疾病的前瞻性风险增加相关（如白细胞介素-27和半乳糖凝集素-9循环水平升高）。我们的研究结果突出了动态生理如何调节心血管疾病生物标志物水平。这些结果还强调了将睡眠时间视为心血管健康关键决定因素的必要性——这一重点反映在最近美国心脏协会的指南中。有必要对女性、老年人、既往有心血管疾病的患者以及不同昼夜节律类型和饮食安排的人群进行进一步研究。
