Tomanek Robert J, Holifield Jennifer S, Reiter Rebecca S, Sandra Alexander, Lin Jim J-C
Department of Anatomy, University of Iowa, Iowa City, Iowa 52242, USA.
Dev Dyn. 2002 Nov;225(3):233-40. doi: 10.1002/dvdy.10158.
The specific roles of vascular endothelial growth factor (VEGF) family members and their receptors (VEGFRs) in coronary vessel formation were studied. By using the quail heart explant model, we found that neutralizing antibodies to VEGF-B or VEGF-C inhibited tube formation on the collagen gel more than anti-VEGF-A. Soluble VEGFR-1, a receptor for VEGF-A and -B, inhibited tube formation by 87%, a finding consistent with that of VEGF-B inhibition. In contrast, addition of soluble VEGFR-2, a receptor for VEGF family members A, C, D, and E, inhibited tube formation by only 43%. Acidic FGF-induced tube formation dependency on VEGF was demonstrated by the attenuating effect of a soluble VEGFR-1 and -2 chimera. The localization of VEGF R-2 and R-3 was demonstrated by in situ hybridization of serial sections, which documented marked accumulations of transcripts for both receptors at the base of the truncus arteriosus coinciding with the temporal and spatial formation of the coronary arteries by means of ingrowth of capillary plexuses. This finding suggests that both VEGFR-2 and R-3 may play a role in the formation of the coronary artery roots. In summary, these experiments document a role for multiple members of the VEGF family and their receptors in formation of the coronary vascular bed.
研究了血管内皮生长因子（VEGF）家族成员及其受体（VEGFRs）在冠状动脉形成中的具体作用。通过使用鹌鹑心脏外植体模型，我们发现，与抗VEGF-A相比，针对VEGF-B或VEGF-C的中和抗体对胶原凝胶上的血管形成抑制作用更强。可溶性VEGFR-1是VEGF-A和VEGF-B的受体，其对血管形成的抑制率达87%，这一结果与VEGF-B抑制实验的结果一致。相比之下，添加可溶性VEGFR-2（VEGF家族成员A、C、D和E的受体）对血管形成的抑制率仅为43%。可溶性VEGFR-1和-2嵌合体的减弱效应证明了酸性成纤维细胞生长因子诱导的血管形成对VEGF的依赖性。通过连续切片的原位杂交显示了VEGF R-2和R-3的定位，其记录了两种受体的转录本在动脉干基部有明显积聚，这与冠状动脉通过毛细血管丛向内生长的时空形成过程相吻合。这一发现表明，VEGFR-2和R-3可能在冠状动脉根部的形成中发挥作用。总之，这些实验证明了VEGF家族的多个成员及其受体在冠状动脉血管床形成中的作用。
