Park Yoon Shin, Kim Nan Hee, Jo Inho
Division of Cardiovascular Research, Department of Biomedical Sciences, National Institute of Health, 5 Nokbun-dong, [122-701], Eunpyung-gu, Seoul, Korea.
Microvasc Res. 2003 Mar;65(2):125-31. doi: 10.1016/s0026-2862(02)00035-3.
The angiopoietin/Tie2 system is a predominant regulator of vascular development. This vascular development appears to be controlled and completed by the coordinated actions of two vascular cells, endothelial cells and their surrounding supporting cells, smooth muscle cells, or pericytes. The role of the angiopoietin/Tie2 system has been studied, but these studies are limited mostly to endothelial cells. In this study, using bovine retinal pericytes (BRP), we investigated the effect of two known angiogenic stimuli, hypoxia and vascular endothelial growth factor (VEGF) treatment, on the regulation of the angiopoietin/Tie2 system. Hypoxia (2% O(2) concentration) was acquired by a hypoxia chamber. Both hypoxia and VEGF (10 ng/ml) treatment significantly increased angiopoietin-1 (Ang1) mRNA expression. This marked augmentation occurred acutely (maximal increase at 2 h) and subsequently decreased. In contrast, angiopoietin-2 (Ang2) mRNA expression was unaltered in BRP upon both treatment. Significant up-regulation of Tie2 mRNA expression was found and lasted up to 12 h. However, using bovine aortic endothelial cells (BAEC), we found that only Ang2 expression, but neither Ang1 nor Tie2, responded to these two angiogenic stimuli, which was consistent with many previous reports. In conclusion, our data suggest that both hypoxia and VEGF treatment differentially regulate the angiopoietin/Tie2 system in the two vascular cells and that, particularly in BRP, the regulation of Ang1, but not Ang2, and Tie2 expression may play an important role in vascular development.
血管生成素/Tie2系统是血管发育的主要调节因子。这种血管发育似乎是由两种血管细胞，即内皮细胞及其周围的支持细胞、平滑肌细胞或周细胞的协同作用来控制和完成的。血管生成素/Tie2系统的作用已得到研究，但这些研究大多局限于内皮细胞。在本研究中，我们使用牛视网膜周细胞（BRP），研究了两种已知的血管生成刺激因素，即缺氧和血管内皮生长因子（VEGF）处理，对血管生成素/Tie2系统调节的影响。通过缺氧箱获得缺氧环境（2%氧气浓度）。缺氧和VEGF（10 ng/ml）处理均显著增加血管生成素-1（Ang1）mRNA表达。这种显著增加在急性时出现（2小时时达到最大增加），随后下降。相比之下，两种处理后BRP中的血管生成素-2（Ang2）mRNA表达未改变。发现Tie2 mRNA表达显著上调，并持续长达12小时。然而，使用牛主动脉内皮细胞（BAEC）时，我们发现只有Ang2表达对这两种血管生成刺激有反应，而Ang1和Tie2均无反应，这与许多先前的报道一致。总之，我们的数据表明，缺氧和VEGF处理在两种血管细胞中对血管生成素/Tie2系统有不同的调节作用，特别是在BRP中，Ang1而非Ang2以及Tie2表达的调节可能在血管发育中起重要作用。
