Anagnostoulis Stavros, Karayiannakis Anastasios J, Lambropoulou Maria, Efthimiadou Anna, Polychronidis Alexandros, Simopoulos Constantinos
Second Department of Surgery, Democritus University of Thrace, Medical School, 68 100 Alexandroupolis, Greece.
Cytokine. 2008 Jun;42(3):353-7. doi: 10.1016/j.cyto.2008.03.009. Epub 2008 Apr 29.
Leptin is an adipocyte-produced peptide, which plays a crucial role in the regulation of body weight. There is also evidence that leptin stimulates endothelial cell proliferation and the formation of capillary-like tubes in vitro. The disc angiogenesis system was used to measure the angiogenic effect of leptin in vivo. Discs containing 25, 50, 100 and 250ng/ml of leptin were implanted subcutaneously in Wistar rats, removed after a growth period of 7 and 14 days, and compared with spontaneous growth controls and with positive controls containing equivalent doses of vascular endothelial growth factor (VEGF). Discs were examined morphologically for stroma and vessel development and by immunohistochemistry for quantitative evaluation of angiogenesis. The specificity of the angiogenic effect of leptin was tested by blocking leptin with a polyclonal anti-leptin antibody. Leptin induced a significant level of angiogenesis in a dose-dependent manner both at 7 and 14 days, with a peak at the dose of 100ng/ml. The angiogenic activity of leptin was completely abolished by the anti-leptin neutralizing antibody. VEGF also induced significant dose-dependent angiogenesis at the same time points with a peak observed at a concentration of 100ng/ml. The angiogenic response to leptin was significantly higher at 7 days compared with VEGF but not at the 14-day time point. In conclusion, leptin has a specific angiogenic effect in vivo, which is dose- and time-dependent in a concentration range of 25-250ng/ml. This effect is equivalent to the angiogenic effect of VEGF but is evident earlier compared with VEGF.
瘦素是一种由脂肪细胞产生的肽，在体重调节中起关键作用。也有证据表明，瘦素在体外能刺激内皮细胞增殖并形成毛细血管样管。采用圆盘血管生成系统来测量瘦素在体内的血管生成作用。将含有25、50、100和250ng/ml瘦素的圆盘皮下植入Wistar大鼠体内，在生长7天和14天后取出，与自发生长对照组以及含有等量血管内皮生长因子（VEGF）的阳性对照组进行比较。对圆盘进行形态学检查以观察基质和血管发育情况，并通过免疫组织化学进行血管生成的定量评估。用多克隆抗瘦素抗体阻断瘦素，以测试瘦素血管生成作用的特异性。瘦素在7天和14天时均以剂量依赖性方式诱导显著水平的血管生成，在100ng/ml剂量时达到峰值。抗瘦素中和抗体完全消除了瘦素的血管生成活性。VEGF在相同时间点也诱导了显著的剂量依赖性血管生成，在浓度为100ng/ml时观察到峰值。与VEGF相比，瘦素在7天时的血管生成反应显著更高，但在14天时则不然。总之，瘦素在体内具有特异性血管生成作用，在25 - 250ng/ml浓度范围内呈剂量和时间依赖性。这种作用等同于VEGF的血管生成作用，但比VEGF更早显现。
