Leptin, the product of Ob gene, promotes angiogenesis
Leptin, the product of Ob gene, promotes angiogenesis
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DOI：
10.1161/01.res.83.10.1059
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发表时间：
1998-11-16
影响因子：
20.1
通讯作者：
Busse, R
中科院分区：
文献类型：
--
作者：
Bouloumié, A;Drexler, HCA;Busse, R
脂肪细胞衍生的细胞因子瘦素被认为在饱腹感和能量消耗的控制中起关键作用。由于脂肪生成和血管生成在脂肪量增加过程中紧密相关，我们检验了瘦素能够调节血管系统生长这一假设。实验使用培养的人脐静脉内皮细胞（HUVECs）和猪主动脉内皮细胞进行。通过蛋白质印迹分析评估了HUVECs中170 - kDa内皮瘦素受体（Ob - R）的存在。使用针对短型和长型Ob - R的特异性寡核苷酸进行的逆转录酶 - 聚合酶链反应分析进一步揭示了内皮细胞中两种Ob - R转录本的表达。此外，瘦素引起了多种内皮蛋白的时间依赖性酪氨酸磷酸化，其中最显著的是丝裂原活化蛋白激酶Erk1/2。用瘦素处理HUVECs导致细胞数量呈浓度依赖性增加，在瘦素浓度为10 ng/mL时达到最大值，且与血管内皮生长因子所引起的增加相当。这种效应与体外血管生成实验中毛细血管样管形成的增强以及体内血管生成模型中的新血管形成相关。这些结果表明，瘦素通过激活内皮Ob - R，产生一种涉及酪氨酸激酶依赖性细胞内途径的生长信号，并促进血管生成过程。我们推测，这种瘦素介导的血管生成刺激可能不仅是肥胖形成的一个关键事件，而且可能在其他组织的生理和病理生理条件下对生长的调节有贡献。
The adipocyte-derived cytokine leptin is thought to play a key role in the control of satiety and energy expenditure. Because adipogenesis and angiogenesis are tightly correlated during the fat mass development, we tested the hypothesis that leptin is able to modulate the growth of the vasculature. Experiments were performed using cultured human umbilical venous endothelial cells (HUVECs) and porcine aortic endothelial cells. The presence of 170-kDa endothelial leptin receptor (Ob-R) was assessed in HUVECs by Western blot analysis. Reverse transcriptase-polymerase chain reaction analysis using specific oligonucleotides for the short and long Ob-R forms further revealed the expression of both Ob-R transcripts in endothelial cells. Moreover, leptin evoked a time-dependent tyrosine phosphorylation of a number of endothelial proteins, the most prominent of which were the mitogen-activated protein kinases Erk1/2. Treatment of HUVECs with leptin led to a concentration-dependent increase in cell number that was maximal at 10 ng/mL leptin and equivalent to that elicited by vascular endothelial growth factor. This effect was associated with an enhanced formation of capillary-like tubes in an in vitro angiogenesis assay and neovascularization in an in vivo model of angiogenesis. These results indicate that leptin, via activation of the endothelial Ob-R, generates a growth signal involving a tyrosine kinase-dependent intracellular pathway and promotes angiogenic processes. We speculate that this leptin-mediated stimulation of angiogenesis might represent not only a key event in the settlement of obesity but also may contribute to the modulation of growth under physiological and pathophysiological conditions in other tissues.