Korff Thomas, Braun Jennifer, Pfaff Dennis, Augustin Hellmut G, Hecker Markus
Institute of Physiology and Pathophysiology, Division of Cardiovascular Physiology, University of Heidelberg, Heidelberg, Germany.
Blood. 2008 Jul 1;112(1):73-81. doi: 10.1182/blood-2007-12-128835. Epub 2008 Apr 29.
Expression of the arterial marker molecule ephrinB2 in endothelial cells is a prerequisite for adequate remodeling processes of the developing or angiogenic vasculature. Although its role in these processes has been extensively studied, the impact of ephrinB2 on the remodeling of adult arteries is largely unknown. To this end, we analyzed its expression during a biomechanically induced arteriolar remodeling process known as arteriogenesis and noted a significant increase in ephrinB2 expression under these conditions. By examining those biomechanical forces presumed to drive arteriogenesis, we identified cyclic stretch as a critical inducer of ephrinB2 expression in endothelial cells. Subsequent functional analyses in vitro revealed that endothelial cells expressing ephrinB2 limit the migration of smooth muscle cells, thereby enhancing segregation of both cell types. Moreover, MCP-1 induced transmigration of monocytes through a monolayer of endothelial cells overexpressing a truncated variant of ephrinB2 was clearly impeded. Taken together, these data suggest that expression of ephrinB2 in adult endothelial cells is up-regulated during arterial remodeling and controlled by cyclic stretch, a well-known inducer of such processes. This stretch-induced ephrinB2 expression may be pivotal for arteriogenesis as it limits smooth muscle cell migration within defined borders and controls monocyte extravasation.
内皮细胞中动脉标志物分子ephrinB2的表达是发育中的或血管生成性脉管系统进行充分重塑过程的前提条件。尽管其在这些过程中的作用已得到广泛研究，但ephrinB2对成年动脉重塑的影响在很大程度上仍不清楚。为此，我们分析了其在一种称为动脉生成的生物力学诱导的小动脉重塑过程中的表达，并注意到在这些条件下ephrinB2表达显著增加。通过研究那些推测驱动动脉生成的生物力学力，我们确定周期性拉伸是内皮细胞中ephrinB2表达的关键诱导因素。随后的体外功能分析表明，表达ephrinB2的内皮细胞限制了平滑肌细胞的迁移，从而增强了两种细胞类型的分离。此外，单核细胞趋化蛋白-1（MCP-1）诱导单核细胞通过过表达ephrinB2截短变体的内皮细胞单层的迁移明显受到阻碍。综上所述，这些数据表明，成年内皮细胞中ephrinB2的表达在动脉重塑过程中上调，并受周期性拉伸控制，而周期性拉伸是此类过程的一个众所周知的诱导因素。这种拉伸诱导的ephrinB2表达可能对动脉生成至关重要，因为它限制了平滑肌细胞在限定边界内的迁移并控制单核细胞外渗。
