Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark;
J Appl Physiol (1985). 2013 Dec;115(12):1777-87. doi: 10.1152/japplphysiol.00979.2013. Epub 2013 Oct 24.
Peripheral arterial disease (PAD) is caused by atherosclerosis and is associated with microcirculatory impairments in skeletal muscle. The present study evaluated the angiogenic response to exercise and passive movement in skeletal muscle of PAD patients compared with healthy control subjects. Twenty-one PAD patients and 17 aged control subjects were randomly assigned to either a passive movement or an active exercise study. Interstitial fluid microdialysate and tissue samples were obtained from the thigh skeletal muscle. Muscle dialysate vascular endothelial growth factor (VEGF) levels were modestly increased in response to either passive movement or active exercise in both subject groups. The basal muscle dialysate level of the angiostatic factor thrombospondin-1 protein was markedly higher (P < 0.05) in PAD patients compared with the control subjects, whereas soluble VEGF receptor-1 dialysate levels were similar in the two groups. The basal VEGF protein content in the muscle tissue samples was ∼27% lower (P < 0.05) in the PAD patients compared with the control subjects. Analysis of mRNA expression for a range of angiogenic and angiostatic factors revealed a modest change with active exercise and passive movement in both groups, except for an increase (P < 0.05) in the ratio of angiopoietin-2 to angiopoietin-1 mRNA in the PAD group with both interventions. PAD patients and aged individuals showed a similar limited angiogenic response to active exercise and passive movement. The limited increase in muscle extracellular VEGF combined with an elevated basal level of thrombospondin-1 in muscle extracellular fluid of PAD patients may restrict capillary growth in these patients.
外周动脉疾病 (PAD) 是由动脉粥样硬化引起的，与骨骼肌微循环损伤有关。本研究评估了 PAD 患者与健康对照者相比，运动和被动运动对骨骼肌的血管生成反应。21 名 PAD 患者和 17 名年龄匹配的对照者被随机分配到被动运动或主动运动研究组。从大腿骨骼肌中获得间质液微透析液和组织样本。在两组受试者中，无论是被动运动还是主动运动，肌肉透析液血管内皮生长因子 (VEGF) 水平都适度增加。与对照组相比，PAD 患者的肌肉透析液中抗血管生成因子血小板反应蛋白-1 蛋白的基础水平明显升高（P < 0.05），而可溶性 VEGF 受体-1 透析液水平在两组间相似。与对照组相比，PAD 患者的肌肉组织样本中的基础 VEGF 蛋白含量低约 27%（P < 0.05）。分析一系列血管生成和抗血管生成因子的 mRNA 表达，发现两组在主动运动和被动运动后都有适度的变化，但 PAD 组在两种干预措施后，血管生成素-2 与血管生成素-1 mRNA 的比值增加（P < 0.05）。PAD 患者和老年人对主动运动和被动运动的血管生成反应相似。肌肉细胞外液中 VEGF 的增加有限，加上 PAD 患者肌肉细胞外液中血小板反应蛋白-1 的基础水平升高，可能限制了这些患者毛细血管的生长。
