Carr Andrew N, Howard Brian W, Yang Hsiao T, Eby-Wilkens Elaine, Loos Paula, Varbanov Alex, Qu Angela, DeMuth Jeffrey P, Davis Michael G, Proia Alan, Terjung Ronald L, Peters Kevin G
Procter and Gamble Pharmaceuticals, Cardiovascular Research Division, Health Care Research Center, Mason, Ohio 45040 USA.
Cardiovasc Res. 2006 Mar 1;69(4):925-35. doi: 10.1016/j.cardiores.2005.12.005. Epub 2006 Jan 10.
Studies have reported that administration of stromal cell-derived factor-1 (SDF-1), the ligand for the G-protein coupled receptor CXCR4, increased collateral blood flow in a mouse model of vascular insufficiency via recruitment of endothelial precursor cells (EPC). The present study investigated the contribution of mature endothelial cells in the actions of SDF-1.
The regulation of SDF-1 and CXCR4 was examined in the rat cornea cauterization (CC) and aortic ring (AR) model. The functional significance of the SDF-1/CXCR4 pathway was explored in cultured endothelial cells, the AR model, and on collateral blood flow in a rat model of vascular insufficiency.
In the present study, the CXCR4 transcript was dramatically upregulated in the rat CC and AR explants, systems containing and lacking bone marrow-derived EPCs, respectively. Addition of AMD3100, a selective CXCR4 antagonist, had no effect on vessel growth in the AR alone, but completely inhibited SDF-1 mediated increases in vascular sprouting. In cultured endothelial cells, SDF-1 alone or in combination with vascular endothelial growth factor (VEGF) significantly enhanced cell survival and migration. Finally, systemic administration of SDF-1 in a rat model of arterial insufficiency enhanced collateral blood flow above vehicle control and equal to that of VEGF after 2 weeks of treatment.
These studies support activation of the SDF-1/CXCR4 axis as a means to promote blood vessel growth and enhance collateral blood flow, at least in part, via direct effects on vascular endothelial cells.
研究报道称，给予基质细胞衍生因子-1（SDF-1），即G蛋白偶联受体CXCR4的配体，可通过募集内皮祖细胞（EPC）增加血管功能不全小鼠模型的侧支血流。本研究调查了成熟内皮细胞在SDF-1作用中的贡献。
在大鼠角膜烧灼（CC）和主动脉环（AR）模型中检测SDF-1和CXCR4的调节情况。在培养的内皮细胞、AR模型以及血管功能不全大鼠模型中探讨SDF-1/CXCR4通路的功能意义。
在本研究中，CXCR4转录本在大鼠CC和AR外植体中显著上调，这两个系统分别含有和缺乏骨髓来源的EPC。添加选择性CXCR4拮抗剂AMD3100对单独的AR血管生长没有影响，但完全抑制了SDF-1介导的血管芽生增加。在培养的内皮细胞中，单独的SDF-1或与血管内皮生长因子（VEGF）联合使用可显著提高细胞存活率和迁移能力。最后，在动脉功能不全大鼠模型中全身给予SDF-1，在治疗2周后，侧支血流增加超过载体对照且与VEGF相当。
这些研究支持激活SDF-1/CXCR4轴作为促进血管生长和增加侧支血流的一种手段，至少部分是通过对血管内皮细胞的直接作用实现的。
