Deindl Elisabeth, Hoefer Imo E, Fernandez Borja, Barancik Miroslav, Heil Matthias, Strniskova Monika, Schaper Wolfgang
Max-Planck-Institute, Department of Experimental Cardiology, Benekestrasse 2, D-61231 Bad Nauheim, Germany.
Circ Res. 2003 Mar 21;92(5):561-8. doi: 10.1161/01.RES.0000061181.80065.7D. Epub 2003 Feb 13.
Fibroblast growth factors (FGFs) have been applied in a variety of therapeutic and experimental studies to improve collateral blood flow. However, the pathophysiological role and the temporospatial expression of the FGFs and their receptors during arteriogenesis have never been elucidated in vivo. Here, we report that collateral artery growth in its early phase is associated with an increased expression of FGF receptor-1 (FGFR-1) and syndecan-4 on mRNA and protein levels as well as with an increased kinase activity of FGFR-1 in a rabbit model of arteriogenesis. However, the mRNA levels of FGF-1 and -2 remained constant. Our data suggest that these growth factors are supplied by endothelial attracted monocytes that, in turn, produce and deliver the FGFs to growing collateral arteries. Monocyte chemoattractant protein-1-stimulated arteriogenesis was strongly reduced in rabbits by application of the FGF inhibitor polyanetholesulfonic acid, indicating that the monocyte-related arteriogenesis (as well as the unstimulated adaptation proper) is promoted by FGFs. In summary, this study shows that arteriogenesis is associated with an increased expression of the FGFRs at the site of the vessel, whereas the growth-promoting ligands are supplied by monocytes in a paracrine way.
成纤维细胞生长因子（FGFs）已被应用于各种治疗和实验研究中，以改善侧支血流。然而，FGFs及其受体在动脉生成过程中的病理生理作用和时空表达在体内尚未得到阐明。在此，我们报告在动脉生成的兔模型中，侧支动脉生长的早期阶段与FGF受体-1（FGFR-1）和syndecan-4在mRNA和蛋白质水平上的表达增加以及FGFR-1激酶活性增加有关。然而，FGF-1和-2的mRNA水平保持恒定。我们的数据表明，这些生长因子由内皮吸引的单核细胞提供，反过来，单核细胞产生并将FGFs递送至生长中的侧支动脉。通过应用FGF抑制剂聚茴香脑磺酸钠，单核细胞趋化蛋白-1刺激的动脉生成在兔中显著降低，表明FGFs促进单核细胞相关的动脉生成（以及未刺激的适应性过程）。总之，本研究表明动脉生成与血管部位FGFRs的表达增加有关，而促进生长的配体由单核细胞以旁分泌方式提供。
