Adipokine resistin promotes in vitro angiogenesis of human endothelial cells
Adipokine resistin promotes in vitro angiogenesis of human endothelial cells
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DOI：
10.1016/j.cardiores.2006.01.015
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发表时间：
2006-04-01
影响因子：
10.8
通讯作者：
Chen, CY
中科院分区：
文献类型：
--
作者：
Mu, H;Ohashi, R;Chen, CY
目的：抵抗素可能与肥胖和心血管疾病有关。然而，抵抗素是否直接促进血管生成尚不清楚。在本研究中，我们评价了抵抗素对血管生成潜能的影响，包括内皮细胞的增殖、迁移和毛细血管样管的形成。方法：用抵抗素处理人冠状动脉内皮细胞。用[H-3]胸腺嘧啶核苷掺入法和NITS法检测细胞增殖。用改良的Boyden小室实验评估细胞迁移。用Matrigel模型研究了毛细管的形成。实时荧光定量聚合酶链式反应(Real-Time-PCR)检测多个基因的表达水平。Bio-Plex Luminex分析仪检测丝裂原活化蛋白激酶(MAPKs)活性。以碱性成纤维细胞生长因子(BFGF)为对照。结果：抵抗素以剂量和时间依赖的方式诱导内皮细胞增殖和迁移，在40 ng/ml时作用最强，抵抗素中和抗体可有效阻断抵抗素诱导的细胞增殖和迁移。此外，抵抗素还能促进HCAECs在Matrigel上形成毛细血管样管。抵抗素还显著上调血管内皮生长因子受体(VEGFR-1和VEGFR-2)和基质金属蛋白酶(MMP1和MMP2)的mRNA表达。此外，在HCAEC中加入抵抗素后，可以观察到ERK1/2和p38的瞬时磷酸化。结论：抵抗素可诱导内皮细胞增殖和迁移，促进毛细血管样管的形成，上调VEGFRs和MMPs的表达，激活ERK1/2和p38通路。因此，抵抗素可能在血管生成相关的血管疾病中发挥重要作用。(C)2006年欧洲心脏病学会。爱思唯尔出版，版权所有。
Objective: Resistin may be associated with obesity and cardiovascular diseases. However, it is unknown whether resistin directly contributes to angiogenesis. In the present study, we evaluated the effects of resistin on angiogenic potential, including endothelial cell proliferation, migration, and capillary-like tube formation.Methods: Human coronary artery endothelial cells (HCAECs) were treated with resistin. Cell proliferation was evaluated by [H-3]thymidine incorporation and NITS assays. Cell migration was assessed by a modified Boyden chamber assay. Capillary-like tube formation was studied with a Matrigel model. Several gene expression levels were determined by real-time PCR. Activation of mitogen-activated protein kinases (MAPKs) was determined by Bio-Plex luminex analyzer. Basic fibroblast growth factor (bFGF) was used as a control. Human umbilical vein endothelial cells (HUVECs) and human lung microvascular endothelial cells (HMVEC-L) were also included.Results: Resistin induced both endothelial proliferation and migration in a dose- and time-dependent manner with the maximal effect at 40 ng/ml. Both resistin-induced cell proliferation and migration could be effectively blocked by a resistin-neutralization antibody. In addition, resistin promoted capillary-like tube formation of HCAECs on Matrigel. Resistin also significantly upregulated the mRNA expression of vascular endothelial growth factor receptors (VEGFR-1 and VEGFR-2) and matrix metalloproteinases (MMP-1 and MMP-2) at both mRNA and protein levels. Furthermore, transient phosphorylation of ERK1/2 and p38 was observed after the addition of resistin to HCAECs. The resistin-induced cell proliferation and migration were both completely blocked by specific ERK1/2 and p38 inhibitors.Conclusions: Resistin induces human endothelial cell proliferation and migration, promotes capillary-like tube formation, upregulates the expression of VEGFRs and MMPs, and activates ERK1/2 and p38 pathways. Thus, resistin may play an important role in angiogenesis-associated vascular disorders. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.