Abstract

FGF2 is a potent stimulator of vascular growth; however, even with a deficiency of FGF2 (Fgf2-/-), developmental vessel growth or ischaemia-induced revascularization still transpires. It remains to be elucidated as to what function, if any, FGF2 has during ischaemic injury. Wildtype (WT) or Fgf2-/- mice were subjected to hindlimb ischaemia for up to 42 days. Limb function, vascular growth, inflammatory- and angiogenesis-related proteins, and inflammatory cell infiltration were assessed in sham and ischaemic limbs at various timepoints. Recovery of ischaemic limb function was delayed in Fgf2-/- mice. Yet, vascular growth response to ischaemia was similar between WT and Fgf2-/- hindlimbs. Several angiogenesis- and inflammatory-related proteins (MCP-1, CXCL16, MMPs and PAI-1) were increased in Fgf2-/- ischaemic muscle. Neutrophil or monocyte recruitment/infiltration was elevated in Fgf2-/- ischaemic muscle. In summary, our study indicates that loss of FGF2 induces a pro-inflammatory microenvironment in skeletal muscle which exacerbates ischaemic injury and delays functional limb use.

摘要

FGF2 是血管生长的有效刺激剂；然而，即使缺乏 FGF2 ( Fgf2-/- )，发育性血管生长或缺血诱导的血运​​重建仍然会发生。FGF2 在缺血性损伤期间具有什么功能（如果有的话）仍有待阐明。野生型 (WT) 或Fgf2-/-小鼠后肢缺血长达 42 天。在不同时间点评估假肢和缺血肢体的肢体功能、血管生长、炎症和血管生成相关蛋白以及炎症细胞浸润。Fgf2-/-小鼠缺血性肢体功能的恢复延迟。然而，WT 和Fgf2-/-后肢对缺血的血管生长反应相似。Fgf2-/-缺血肌肉中多种血管生成和炎症相关蛋白（MCP-1、CXCL16、MMP 和 PAI-1）增加。Fgf2-/-缺血性肌肉中中性粒细胞或单核细胞募集/浸润升高。总之，我们的研究表明，FGF2 的缺失会导致骨骼肌中产生促炎性微环境，从而加剧缺血性损伤并延迟肢体功能使用。