Department of Medicine, Johns Hopkins University, Division of Pulmonary and Critical Care Medicine, Baltimore, MD 21224, USA.
Microvasc Res. 2010 Jul;80(1):18-22. doi: 10.1016/j.mvr.2010.01.011. Epub 2010 Feb 6.
We showed previously in a mouse model of lung ischemia-induced angiogenesis, enhanced expression of the three ELR+ CXC chemokines (KC, LIX, and MIP-2) and that blockade of the ligand receptor CXCR(2) limited neovascularization. The present study was undertaken to determine the relative abundance and angiogenic potential of the three CXC chemokines and whether RhoA activation explained the measured differences in potencies. We found that LIX showed the greatest absolute amount in the in vivo model 4 h after left pulmonary artery obstruction (LIX>KC>MIP-2; p<0.05). In vitro, LIX induced the greatest degree of arterial endothelial cell chemotaxis and KC was without effect. A significant increase (approximately 40%) in active RhoA was observed with both LIX and MIP-2 compared with vehicle control (p<0.05). On average, LIX induced the greatest amount of tube formation within pleural tissue in culture. Thus, the results of the present study suggest that among the three ELR+ CXC chemokines, LIX predominates in eliciting a pro-angiogenic phenotype.
我们之前在肺缺血诱导血管生成的小鼠模型中表明，三种 ELR+CXC 趋化因子（KC、LIX 和 MIP-2）的表达增强，并且趋化因子受体 CXCR(2)的阻断限制了新血管生成。本研究旨在确定三种 CXC 趋化因子的相对丰度和血管生成潜力，以及 RhoA 激活是否可以解释所测量的效力差异。我们发现，在左肺动脉阻塞后 4 小时的体内模型中，LIX 表现出最大的绝对量（LIX>KC>MIP-2；p<0.05）。在体外，LIX 诱导动脉内皮细胞趋化作用的程度最大，而 KC 则没有作用。与载体对照相比，LIX 和 MIP-2 观察到活性 RhoA 显著增加（约 40%）（p<0.05）。平均而言，LIX 在胸膜组织中诱导的管形成量最大。因此，本研究的结果表明，在这三种 ELR+CXC 趋化因子中，LIX 在引发促血管生成表型方面占主导地位。
