Department of Pediatrics, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, P.O.B. 151, 84101, Beer Sheva, Israel.
Pediatric Pulmonary and Sleep Research Laboratory, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel.
Sci Rep. 2020 Dec 17;10(1):22115. doi: 10.1038/s41598-020-79187-0.
Obstructive sleep apnea syndrome (OSA) is associated with cardiovascular morbidity in adults and children. NFκB activity is enhanced in circulating monocytes of adults with OSA, that decreases following positive pressure therapy. OSA children's serum activates NFκB in a cell line. We hypothesized that OSA children's serum can activate NFκB in cardiomyocytes (CM) and effect their viability. In order to explore the role played by NFκB in OSA cardiovascular pathophysiology, rat, mouse and human immortalized CM were exposed to human serum drawn from OSA children and matched controls. Increased expression of NFκB classical subunits p65/p50 as well as major morphological changes occurred in cardiomyocytes following OSA's serum exposure. OSA children's serum induced NFκB activity as measured by p65 nuclear translocation in immortalized human CM and rat cardiomyocytes as well as dense immunostaining of the nucleus. Trypan blue and XTT assays showed that OSA sera induced CM apoptosis. We conclude that NFκB is systemically activated in cardiomyocytes, who also demonstrate decreased viability and contractility following exposure to OSA serum. It supports the hypothesis NFκB plays a role in the evolution of cardiovascular morbidity in OSA. It may support the search for new therapeutic interventions controlling NFκB activation in OSA.
阻塞性睡眠呼吸暂停综合征（OSA）与成年人和儿童的心血管发病率有关。患有 OSA 的成年人循环单核细胞中的 NFκB 活性增强，经正压治疗后降低。OSA 儿童的血清可在细胞系中激活 NFκB。我们假设 OSA 儿童的血清可以激活心肌细胞（CM）中的 NFκB 并影响其活力。为了探讨 NFκB 在 OSA 心血管病理生理学中的作用，用取自 OSA 儿童和匹配对照的人血清孵育大鼠、小鼠和人永生化 CM。心肌细胞暴露于 OSA 血清后，NFκB 经典亚基 p65/p50 的表达增加以及主要形态发生变化。OSA 儿童的血清诱导 NFκB 活性，如在永生化人 CM 和大鼠心肌细胞中 p65 核易位以及核密集免疫染色所测量的那样。台盼蓝和 XTT 测定表明 OSA 血清诱导 CM 凋亡。我们得出结论，NFκB 在心肌细胞中被系统性激活，并且在暴露于 OSA 血清后，心肌细胞的活力和收缩性也降低。这支持了 NFκB 在 OSA 心血管发病率演变中起作用的假说。它可能支持寻找新的治疗干预措施来控制 OSA 中 NFκB 的激活。
