CNRS, LIPhy, Université Grenoble Alpes, 38000 Grenoble, France.
Shenzhen Sibionics Co. Ltd, Shenzhen, People's Republic of China.
J R Soc Interface. 2023 Jul;20(204):20230186. doi: 10.1098/rsif.2023.0186. Epub 2023 Jul 19.
ATP is not only an energy carrier but also serves as an important signalling molecule in many physiological processes. Abnormal ATP level in blood vessel is known to be related to several pathologies, such as inflammation, hypoxia and atherosclerosis. Using advanced numerical methods, we analysed ATP released by red blood cells (RBCs) and its degradation by endothelial cells (ECs) in a cat mesentery-inspired vascular network, accounting for RBC mutual interaction and interactions with vascular walls. Our analysis revealed a heterogeneous ATP distribution in the network, with higher concentrations in the cell-free layer, concentration peaks around bifurcations and heterogeneity among vessels of the same level. These patterns arise from the spatio-temporal organization of RBCs induced by the network geometry. It is further shown that an alteration of hematocrit and flow strength significantly affects ATP level as well as heterogeneity in the network. These findings constitute a first building block to elucidate the intricate nature of ATP patterns in vascular networks and the far reaching consequences for other biochemical signalling, such as calcium, by ECs.
ATP 不仅是一种能量载体,在许多生理过程中也是一种重要的信号分子。已知血管中异常的 ATP 水平与几种病理有关,如炎症、缺氧和动脉粥样硬化。我们使用先进的数值方法,分析了在猫肠系膜启发的血管网络中红细胞 (RBC) 释放的 ATP 及其被内皮细胞 (EC) 降解的情况,同时考虑了 RBC 之间的相互作用以及与血管壁的相互作用。我们的分析揭示了网络中存在不均匀的 ATP 分布,在无细胞层中浓度较高,在分叉处出现浓度峰值,并且同一水平的血管之间存在异质性。这些模式是由网络几何形状引起的 RBC 的时空组织产生的。进一步表明,血细胞比容和流动强度的改变显著影响网络中的 ATP 水平和异质性。这些发现构成了阐明血管网络中 ATP 模式的复杂性质以及对 EC 中其他生化信号(如钙)的深远影响的第一个基石。