Traffic Patterns of the Migrating Endothelium: How Force Transmission Regulates Vascular Malformation and Functional Shunting During Angiogenic Remodelling.
Traffic Patterns of the Migrating Endothelium: How Force Transmission Regulates Vascular Malformation and Functional Shunting During Angiogenic Remodelling.
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DOI：
10.3389/fcell.2022.840066
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发表时间：
2022
影响因子：
5.5
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中科院分区：
文献类型：
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血管生成发生在不同的阶段：最初的喷出之后是重塑，其中组成血管的内皮细胞（EC）通过逆流动方向迁移而重新排列。异常重塑可导致血管畸形。这就是小鼠视网膜内Alk 1受体突变的情况，其破坏了血流-迁移偶联，产生了与血流极化/逆血流极化的EC混合群体，这些EC聚集成动静脉畸形（AVM）。缺乏活体成像选择意味着驱动AVM的集体EC动态和极性混合群体的后果仍然是一个谜。因此，我们的目标是提出一种新的代理为基础的模型，提供理论上的洞察EC力传输和集体动力学血管生成重塑过程中。相邻代理之间的力传递包括保持间距的挤压力和保持集体的凝聚力。我们进行了迁移模拟均匀极化人口（反对流动）和混合极性（与/反对流动）。在均匀极化的群体内，挤压力通过促进EC嵌入来稳定丛，这确保细胞保持均匀分布。过度的内聚破坏嵌入，导致细胞聚集和功能分流。EC之间的过度凝聚力阻止它们解决丛内的直径平衡，导致长时间的流动逆转，这在系统内产生关键的行为变化，因为它们在分叉处切换细胞迁移和交通模式的方向。引入细胞极性的混合物极大地改变了系统内挤压力的作用。在低挤出时，相对的EC能够彼此移动;然而，在高挤出时，细胞之间的推动导致迁移速度接近于零，形成交通堵塞并破坏迁移。在我们的研究中，我们产生了血管畸形和功能性分流，无论是内皮细胞之间的过度凝聚力或细胞极性的混合物。这两种机制的中心是细胞-细胞粘附连接，其参与流动感测/极性，并且必须动态重塑以允许血管图案化期间细胞的重排。因此，我们的研究结果表明，连接功能障碍是治疗和预防血管疾病和AVM的新靶点。
Angiogenesis occurs in distinct phases: initial spouting is followed by remodelling in which endothelial cells (ECs) composing blood vessels rearrange by migrating against the direction of flow. Abnormal remodelling can result in vascular malformation. Such is the case in mutation of the Alk1 receptor within the mouse retina which disrupts flow-migration coupling, creating mixed populations of ECs polarised with/against flow which aggregate into arteriovenous malformations (AVMs). The lack of live imaging options in vivo means that the collective EC dynamics that drive AVM and the consequences of mixed populations of polarity remain a mystery. Therefore, our goal is to present a novel agent-based model to provide theoretical insight into EC force transmission and collective dynamics during angiogenic remodelling. Force transmission between neighbouring agents consists of extrusive forces which maintain spacing and cohesive forces which maintain the collective. We performed migration simulations within uniformly polarised populations (against flow) and mixed polarity (with/against flow). Within uniformly polarised populations, extrusive forces stabilised the plexus by facilitating EC intercalation which ensures that cells remained evenly distributed. Excess cohesion disrupts intercalation, resulting in aggregations of cells and functional shunting. Excess cohesion between ECs prevents them from resolving diameter balances within the plexus, leading to prolonged flow reversals which exert a critical behaviour change within the system as they switch the direction of cell migration and traffic patterns at bifurcations. Introducing mixtures of cell polarity dramatically changed the role of extrusive forces within the system. At low extrusion, opposing ECs were able to move past each other; however, at high extrusion the pushing between cells resulted in migration speeds close to zero, forming traffic jams and disrupting migration. In our study, we produced vascular malformations and functional shunting with either excess cohesion between ECs or mixtures of cell polarity. At the centre of both these mechanisms are cell-cell adherens junctions, which are involved in flow sensing/polarity and must remodelling dynamically to allow rearrangements of cells during vascular patterning. Thus, our findings implicate junctional dysfunction as a new target in the treatment and prevention of vascular disease and AVMs.
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影响因子：
9.8
作者：
Franco CA;Jones ML;Bernabeu MO;Geudens I;Mathivet T;Rosa A;Lopes FM;Lima AP;Ragab A;Collins RT;Phng LK;Coveney PV;Gerhardt H
通讯作者：
Gerhardt H
影响因子：
3.3
作者：
Baeyens N;Schwartz MA
通讯作者：
Schwartz MA
脑动力畸形破裂：手术时机和结局 - 对25例的回顾性研究。
影响因子：
1.4
作者：
Di Bartolomeo A;Scafa AK;Giugliano M;Dugoni DE;Ruggeri AG;Delfini R
通讯作者：
Delfini R
影响因子：
3.4
作者：
Bernabeu MO;Jones ML;Nash RW;Pezzarossa A;Coveney PV;Gerhardt H;Franco CA
通讯作者：
Franco CA
影响因子：
7.7
作者：
Carvalho, Joana R.;Fortunato, Isabela C.;Franco, Claudio A.
通讯作者：
Franco, Claudio A.