Müller Nicole, Hart Christopher, Härtel Julian Alexander, Jordan Jens, Tank Jens, Breuer Johannes, Grau Marijke, Frede Stilla, Splettstoesser Frank, Kratz Tobias
Department of Pediatric Cardiology, University Hospital Bonn, 53127 Bonn, Germany.
Department of Molecular and Cellular Sports Medicine, German Sport University Cologne, 50933 Cologne, Germany.
Int J Mol Sci. 2025 Jan 21;26(3):887. doi: 10.3390/ijms26030887.
Patients with a univentricular heart live with chronic hypoxia (75-85%) in their first years of life, which could affect adaptation to altitude or other hypoxic insults later in life. To test this hypothesis, we exposed 18 patients with Fontan circulation (age: 24.5 [16.3-38.8] years; f/m 9/9) to simulated altitude using normobaric hypoxia (15.2% oxygen, equivalent to 2500 masl) for 24 h. In blood samples obtained in normoxia (T1, 21% oxygen) and after 24 h hypoxia after a submaximal stress test, we measured hypoxia-regulated molecules involved in angiogenesis and tissue homeostasis. A significant increase was displayed for IL-10 ( = 0.001), CCL2 ( = 0.006), ANG-1 ( = 0.001), ANG-2 ( = 0.029), FGF-1 ( = 0.001) and FGF-2 ( = 0.024). E-Selectin ( < 0.001) and NRG-1 were significantly different at = 0.026 at T2 compared to baseline. However, OPN and OSF-1 did not exhibit significant changes ( = 0.348; = 0.065). Fontan patients show hypoxia-related protein patterns similar to healthy individuals despite intermittent hypoxemia, but their response to standardised hypoxia was described here for the first time, requiring further study.
单心室心脏患者在生命的最初几年中存在慢性缺氧(75 - 85%),这可能会影响其日后对高原环境或其他缺氧刺激的适应能力。为了验证这一假设,我们让18例具有Fontan循环的患者(年龄:24.5 [16.3 - 38.8]岁;男/女9/9)通过常压缺氧(15.2%氧气,相当于海拔2500米)模拟高原环境24小时。在常氧(T1,21%氧气)下以及次极量运动试验后缺氧24小时采集的血样中,我们检测了参与血管生成和组织稳态的缺氧调节分子。IL - 10(P = 0.001)、CCL2(P = 0.006)、ANG - 1(P = 0.001)、ANG - 2(P = 0.029)、FGF - 1(P = 0.001)和FGF - 2(P = 0.024)均有显著升高。与基线相比,T2时E - 选择素(P < 0.001)和NRG - 1在P = 0.026时有显著差异。然而,OPN和OSF - 1未表现出显著变化(P = 0.348;P = 0.065)。尽管存在间歇性低氧血症,但Fontan患者显示出与健康个体相似的缺氧相关蛋白模式,不过本文首次描述了他们对标准化缺氧的反应,这需要进一步研究。