Paar Vera, Boxhammer Elke, Marmullaku Fitore, Hoppe Uta C, Lichtenauer Michael, Jirak Peter
Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria.
Department of Internal Medicine II, Division of Cardiology, Paracelsus Medical University of Salzburg, 5020 Salzburg, Austria.
Life Sci Space Res (Amst). 2025 Aug;46:115-127. doi: 10.1016/j.lssr.2025.04.002. Epub 2025 Apr 4.
This study aimed to examine the effects of weightlessness and microgravity, induced by parabolic flight, on specific biomarkers associated with angiogenesis, lipid homeostasis, and cardiovascular diseases, including angiogenin (ANG), angiopoietin-1 (ANGPT-1), angiopoietin-like protein 4 (ANGPTL4), heat shock protein 70 (HSP70), transforming growth factor-beta (TGF-β), vascular endothelial growth factor (VEGF), and platelet-derived growth factor subunit AA (PDGF-AA). 14 healthy volunteers (mean age: 28.9 years; 6 females) participated in short-term sessions of weightlessness and microgravity using parabolic flights. Venous blood samples were collected at different time points (baseline, 1 h, and 24 h after parabolic flight) and frozen as serum samples. Initially, Proteome Profiler Angiogenesis Array was used to screen pooled serum samples of each time point for potential alterations of angiogenesis-associated proteins. Additionally, individual blood samples were analyzed using enzyme-linked immunosorbent assay (ELISA). Proteome Arrays revealed an overall decrease of angiogenesis-associated proteins in response to parabolic flight. On the other hand, proteins associated with lipid homeostasis, such as Leptin and TIMP-4, were significantly elevated in response to parabolic flight. Individual analysis of selected proteins solely revealed a slight increase of ANGPTL4 and HSP70 levels 1 hour post-flight, although without statistical significance (p = 0.7705). Nevertheless, 24 h after parabolic flight, ANGPTL4 concentrations in serum significantly decreased compared to the preceding time point (p = 0.0020). Similarly, HSP70 was tendentially elevated 1 h after flight (p = 0.8135), though significantly declined at the end of the experiment (BL vs. 24 h: p = 0.0435; 1 h vs. 24 h: p = 0.0031). No significant differences could be observed in ANG, ANGPT1, TGF-β1, VEGF, and PDGF-AA concentrations at any time point. The findings of this study suggest that exposure to gravitational changes, such as weightlessness and microgravity, may lead to relevant changes in angiogenesis and lipid homeostasis. The upregulation of Leptin and TIMP-4, as well as ANGPTL4 in short-term response to parabolic flight poses a risk to disturbances in lipid metabolism, potentially increasing the likelihood of cardiovascular or hepatic events. Further research is needed to better understand the impact of microgravity and weightlessness on angiogenesis and lipid metabolism to protect astronaut health during prolonged space missions.
本研究旨在探讨抛物线飞行诱导的失重和微重力对与血管生成、脂质稳态及心血管疾病相关的特定生物标志物的影响，这些生物标志物包括血管生成素（ANG）、血管生成素-1（ANGPT-1）、血管生成素样蛋白4（ANGPTL4）、热休克蛋白70（HSP70）、转化生长因子-β（TGF-β）、血管内皮生长因子（VEGF）和血小板衍生生长因子亚基AA（PDGF-AA）。14名健康志愿者（平均年龄：28.9岁；6名女性）参与了使用抛物线飞行进行的短期失重和微重力实验。在不同时间点（抛物线飞行前基线、飞行后1小时和24小时）采集静脉血样，并作为血清样本冷冻保存。最初，使用蛋白质组分析血管生成阵列筛选每个时间点的混合血清样本中血管生成相关蛋白的潜在变化。此外，使用酶联免疫吸附测定（ELISA）分析个体血样。蛋白质组阵列显示，抛物线飞行后血管生成相关蛋白总体减少。另一方面，与脂质稳态相关的蛋白，如瘦素和金属蛋白酶组织抑制因子-4（TIMP-4），在抛物线飞行后显著升高。对选定蛋白的个体分析仅显示飞行后1小时ANGPTL4和HSP70水平略有升高，尽管无统计学意义（p = 0.7705）。然而，抛物线飞行后24小时，血清中ANGPTL4浓度与前一时间点相比显著降低（p = 0.0020）。同样，HSP70在飞行后1小时有升高趋势（p = 0.8135），但在实验结束时显著下降（基线与24小时：p = 0.0435；1小时与24小时：p = 0.0031）。在任何时间点，ANG、ANGPT1、TGF-β1、VEGF和PDGF-AA浓度均未观察到显著差异。本研究结果表明，暴露于失重和微重力等重力变化可能导致血管生成和脂质稳态发生相关变化。瘦素、TIMP-4以及抛物线飞行短期反应中的ANGPTL4上调对脂质代谢紊乱构成风险，可能增加心血管或肝脏事件的发生可能性。需要进一步研究以更好地了解微重力和失重对血管生成和脂质代谢的影响，从而在长期太空任务中保护宇航员健康。
