Aitsebaomo Julius, Portbury Andrea L, Schisler Jonathan C, Patterson Cam
Division of Cardiology and Carolina Cardiovascular Biology Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7126, USA.
Circ Res. 2008 Oct 24;103(9):929-39. doi: 10.1161/CIRCRESAHA.108.184937.
The molecular differences between arteries and veins are genetically predetermined and are evident even before the first embryonic heart beat. Although ephrinB2 and EphB4 are expressed in cells that will ultimately differentiate into arteries and veins, respectively, many other genes have been shown to play a significant role in cell fate determination. The expression patterns of ephrinB2 and EphB4 are restricted to arterial-venous boundaries, and Eph/ephrin signaling provides repulsive cues at arterial-venous boundaries that are thought to prevent intermixing of arterial- and venous-fated cells. However, the maintenance of arterial-venous fate is susceptible to some degree of plasticity. Thus, in response to signals from the ambient microenvironment and shear stress, there is flow-mediated intercalation of the arteries and veins that ultimately leads to the formation of a functional, closed-loop circulation. In addition, cells in the blood vessels of each organ undergo epigenetic, morphological, and functional adaptive changes that are specific to the proximate function of their cognate organ(s). These adaptive changes result in an interorgan and intraorgan vessel heterogeneity that manifest clinically in a disparate response of different organs to identical risk factors and injury in the same animal. In this review, we focus on the molecular and physiological factors influencing arterial-venous heterogeneity between and within different organ(s). We explore arterial-venous differences in selected organs, as well as their respective endothelial cell architectural organization that results in their inter- and intraorgan heterogeneity.
动脉和静脉之间的分子差异在基因上是预先确定的，甚至在胚胎第一次心跳之前就很明显。尽管 EphrinB2 和 EphB4 分别在最终分化为动脉和静脉的细胞中表达，但许多其他基因已被证明在细胞命运决定中起重要作用。EphrinB2 和 EphB4 的表达模式局限于动静脉边界，Eph/ephrin 信号在动静脉边界提供排斥信号，被认为可防止动脉和静脉命运的细胞相互混合。然而，动静脉命运的维持在一定程度上易受可塑性影响。因此，响应来自周围微环境和剪切应力的信号，动脉和静脉会发生血流介导的嵌入，最终导致功能性闭环循环的形成。此外，每个器官血管中的细胞会经历表观遗传、形态和功能上的适应性变化，这些变化特定于其相关器官的邻近功能。这些适应性变化导致器官间和器官内血管的异质性，在临床上表现为同一动物体内不同器官对相同风险因素和损伤的不同反应。在本综述中，我们重点关注影响不同器官之间以及器官内部动静脉异质性的分子和生理因素。我们探讨选定器官中的动静脉差异，以及导致其器官间和器官内异质性的各自内皮细胞结构组织。
