Schierling Wilma, Troidl Kerstin, Troidl Christian, Schmitz-Rixen Thomas, Schaper Wolfgang, Eitenmüller Inka K
Max Planck Institute for Heart and Lung Research, Bad Nauheim, Germany.
J Vasc Res. 2009;46(4):365-74. doi: 10.1159/000189797. Epub 2009 Jan 10.
BACKGROUND/AIMS: Collateral vessels restore only about 40% of the maximum dilatory reserve after femoral artery occlusion, whereas complete normalization is reached by increased fluid shear stress (FSS). We studied the role of known potent angiogenic growth factors (separately or in combination) in arteriogenesis by determining their expression in FSS-stimulated collaterals and close-to-collateral infusion of growth factor peptides in a rabbit model of femoral artery occlusion.
Values of maximum collateral conductance (C(max)) and post mortem angiograms were compared to those achievable by high FSS. mRNA levels of growth factor ligands and receptors were determined in FSS-stimulated collaterals.
Seven days after vessel occlusion, FSS-stimulated legs showed a C(max) not significantly different from that of not occluded femoral arteries. Arteriogenesis was significantly less enhanced after growth factor treatment (MCP-1 86%, Ad5.1-FGF-4 75%, bFGF 72%, PDGF 64%, VEGF 50% of C(max) after FSS stimulation). RT-PCR showed no differential expression of FGF receptors, but an up-regulation of VEGF-receptor-2.
The most potent known angiogenic growth factors at high pharmacological doses reach only a fraction of the maximum conductance obtained by high FSS. Arteriogenesis differs from angiogenesis, so the main focus to markedly improve arteriogenesis should be put on the underlying mechanisms of shear stress.
背景/目的：股动脉闭塞后，侧支血管仅能恢复约40%的最大扩张储备，而增加流体切应力（FSS）可使其完全恢复正常。我们通过测定已知强效血管生成生长因子在FSS刺激的侧支血管中的表达以及在股动脉闭塞兔模型中向侧支血管附近输注生长因子肽，研究了这些生长因子（单独或联合使用）在动脉生成中的作用。
将最大侧支血管传导率（C(max)）值和死后血管造影结果与高FSS所能达到的值进行比较。测定FSS刺激的侧支血管中生长因子配体和受体的mRNA水平。
血管闭塞7天后，FSS刺激的腿部C(max)与未闭塞的股动脉无显著差异。生长因子治疗后动脉生成的增强明显较少（MCP-1为FSS刺激后C(max)的86%，Ad5.1-FGF-4为75%，bFGF为72%，PDGF为64%，VEGF为50%）。RT-PCR显示FGF受体无差异表达，但VEGF受体-2上调。
在高药理剂量下，已知最强效的血管生成生长因子只能达到高FSS所获得的最大传导率的一部分。动脉生成不同于血管生成，因此显著改善动脉生成的主要重点应放在切应力的潜在机制上。
