ANGIOGENIC GROWTH FACTORS IN EXERCISING SKELETAL MUSCLE

运动刺激骨骼肌血管新生。 毛细血管的增加改善了周围动脉功能不全（派）患者的肌肉功能和生活质量。因此，运动训练或促血管生成药物治疗（如果运动是禁忌）可能对这些患者有帮助。 然而，参与骨骼肌血管生成的生长因子、受体和信号传导通路还没有很好的表征。 因此，这些研究将解决三个具体的目的：1）表征在运动训练计划期间正常大鼠和后肢缺血大鼠的红色和白色腓肠肌中血管生成生长因子的含量和表达的变化的时间过程;（二）表征红色和白色腓肠肌中血管生成生长因子受体含量和表达变化的时间过程在运动训练计划期间，正常大鼠和后肢缺血大鼠的肌肉;和3）确定功能性一氧化氮信号通路或血管生成素/Tie-2系统是否对运动刺激的血管生成是必需的。 这些研究将利用股动脉结扎大鼠，一种派模型。 大鼠将遵循一个跑步机锻炼计划，已知刺激血管生成。 对于特定目的1和2，将在血管扩张的初始阶段（28天）评估生长因子（VEGF、bFGF、血管生成素-1和血管生成素-2）及其受体的水平，并将其与毛细血管生长相关。 对于特定目标3，将在约2周运动后评价一氧化氮合酶或Tie-2（血管生成素受体）抑制对毛细血管生长和细胞增殖的影响。 这些研究将促进对骨骼肌血管生成的理解，并可能为派患者提供治疗建议。

Exercise stimulates angiogenesis in skeletal muscle. The increased capillarity improves muscle function and quality of life in patients with peripheral arterial insufficiency (PAI). Thus, either exercise training or proangiogenic drug therapies (if exercise is contraindicated) could be helpful to these patients. However, the growth factors, receptors, and signaling pathways involved in skeletal muscle angiogenesis are not well characterized. Therefore, these studies will address three Specific Aims: 1) to characterize the time course of alterations in the content and expression of angiogenic growth factors in red and white gastrocnemius muscle of both normal rats and rats with hindlimb ischemia during an exercise training program; 2) to characterize the time course of alterations in the content and expression of receptors for angiogenic growth factors in red and white gastrocnemius muscle of both normal rats and rats with hindlimb ischemia during an exercise training program; and 3) to determine whether a functioning nitric oxide signaling pathway or the angiopoietin/Tie-2 system is essential for exercise- stimulated angiogenesis. These studies will utilize femorally- ligated rats, a model of PAI. Rats will follow a treadmill exercise program known to stimulate angiogenesis. For Specific Aims 1 and 2, levels of growth factors (VEGF, bFGF, angiopoietin- 1, and angiopoietin-2) and their receptors will be assessed over the initial period of vascular expansion (28 d) and correlated with capillary growth. For Specific Aim 3, the effect of nitric oxide synthase or Tie-2 (angiopoietin receptor) inhibition on capillary growth and cell proliferation will be evaluated following approximately 2 w of exercise. These studies will advance understanding of skeletal muscle angiogenesis and may suggest treatments for patients with PAI.