le Noble F, Fleury V, Pries A, Corvol P, Eichmann A, Reneman R S
Collège de France, Laboratoire de Médecine Expérimentale, Inserm U36, 11 Place Marcelin Berthelot, Paris 75231, France.
Cardiovasc Res. 2005 Feb 15;65(3):619-28. doi: 10.1016/j.cardiores.2004.09.018.
Formation of a properly branched vascular system during embryogenesis is crucial for embryo survival. Here we review the regulation of the morphogenesis of the arterial and venous system during embryogenesis. We show that in addition to deterministic patterning mechanisms and plasticity of endothelial cells, arterial-venous differentiation and branching morphogenesis involves a prominent role for blood flow. Based on in vivo observations of developing arteries, we identified a novel morphological event crucial for the morphogenesis of the arterial tree, disconnection of small side branches. This disconnection of side branches occurs exactly at the point of bifurcation. The rate of disconnection of side branches depends on flow velocity and branching angle. The balance between disconnection and maintenance of arterial side branches determines the number of side branches connected to a large artery. Based on these observations, we postulate that the number of pre-existing collaterals connected to a large artery is a function of the disconnection process and can be regulated by hemodynamics. We furthermore show that embryonic arteries already adapt their lumen diameter to the amount of flow carried. Taken together, we suggest that hemodynamics plays a pivotal role in shaping the arterial system. We suggest that flow-evoked remodeling processes determine the number of preexisting collaterals during critical periods of embryo-fetal development. Insight into these basic principles of arterial growth and branching during embryogenesis may aid to understanding the observed variability in the capacity to establish a collateral circulation in patients with ischemic diseases and finding new strategies for therapeutic arteriogenesis.
胚胎发育过程中形成正常分支的血管系统对胚胎存活至关重要。在此，我们综述胚胎发育过程中动脉和静脉系统形态发生的调控。我们发现，除了确定性的模式形成机制和内皮细胞的可塑性外，动静脉分化和分支形态发生还涉及血流的重要作用。基于对发育中动脉的体内观察，我们确定了一个对动脉树形态发生至关重要的新形态学事件，即小侧支的断开。侧支的这种断开恰好发生在分叉点。侧支断开的速率取决于流速和分支角度。动脉侧支断开与维持之间的平衡决定了连接到一条大动脉的侧支数量。基于这些观察结果，我们推测连接到一条大动脉的预先存在的侧支数量是断开过程的一个函数，并且可以由血流动力学调节。我们还表明，胚胎动脉已经使其管腔直径适应所携带的血流量。综上所述，我们认为血流动力学在塑造动脉系统中起关键作用。我们认为，血流诱发的重塑过程在胚胎 - 胎儿发育的关键时期决定了预先存在的侧支数量。深入了解胚胎发育过程中动脉生长和分支的这些基本原理，可能有助于理解缺血性疾病患者建立侧支循环能力的观察到的变异性，并找到治疗性动脉生成的新策略。
