Gigante Bruna, Tarsitano Marina, Cimini Vincenzo, De Falco Sandro, Persico M Graziella
Institute of Genetics and Biophysics Adriano Buzzati-Traverso, CNR, Naples, Italy.
Angiogenesis. 2004;7(3):277-84. doi: 10.1007/s10456-004-4179-1.
Angiogenesis is a tightly regulated process, both during development and adult life. Animal models with mutations in the genes coding for placental growth factor (PlGF), a member of vascular endothelial growth factor (VEGF) family, or the tyrosine kinase domain of the PlGF receptor (Flt-1) have revealed differences between normal physiological angiogenesis and pathological angiogenesis associated with conditions such as tumor growth, arthritis and atherosclerosis. In the present paper, we investigated the potential role of PlGF in regulating physiological angiogenesis by analyzing vascular changes in heart and skeletal muscles of wild-type and Plgf-/- mice following prolonged and sustained physical training. Sedentary Plgf-/- mice showed a reduced capillary density in both heart and skeletal muscles as compared to wild-type mice (P < 0.05). However, after a 6-week training period, heart/body weight ratio, citrate synthase activity, vessel density and capillary/myocyte ratio were significantly increased in both wild-type and Plgf-/- mice (all P < 0.05). At the same time intercapillary distance was significantly reduced. Finally, acute exercise was not associated with any change in PlGF protein level in the skeletal muscle. Our results demonstrate that PlGF is not necessary for exercise-training-induced angiogenesis. We thus suggest that the role of PlGF is confined to the selective regulation of angiogenesis only under pathological conditions.
血管生成是一个在发育过程和成年期都受到严格调控的过程。在编码胎盘生长因子（PlGF，血管内皮生长因子（VEGF）家族的一员）或PlGF受体（Flt-1）酪氨酸激酶结构域的基因发生突变的动物模型中，已揭示出正常生理血管生成与与肿瘤生长、关节炎和动脉粥样硬化等病症相关的病理性血管生成之间的差异。在本文中，我们通过分析野生型和Plgf-/-小鼠在长期持续体育训练后心脏和骨骼肌中的血管变化，研究了PlGF在调节生理血管生成中的潜在作用。与野生型小鼠相比，久坐不动的Plgf-/-小鼠心脏和骨骼肌中的毛细血管密度均降低（P < 0.05）。然而，经过6周的训练期后，野生型和Plgf-/-小鼠的心脏/体重比、柠檬酸合酶活性、血管密度和毛细血管/肌细胞比均显著增加（均P < 0.05）。同时，毛细血管间距显著减小。最后，急性运动与骨骼肌中PlGF蛋白水平的任何变化均无关。我们的结果表明，PlGF对于运动训练诱导的血管生成并非必需。因此，我们认为PlGF的作用仅局限于在病理条件下对血管生成的选择性调节。
