Adipokine resistin promotes in vitro angiogenesis of human endothelial cells

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 [3H]thymidine incorporation and MTS 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.

Mu, Hong
Ohashi, Ryuji
Yan, Shaoyu
Chai, Hong
Yang, Hui
Lin, Peter
Yao, Qizhi
Chen, Changyi
Item Type: 
Journal Article
Publication Title: 
Cardiovascular Research
Journal Abbreviation: 
Cardiovasc. Res.
Publication Date: 
Apr 1, 2006
Publication Year: 
Library Catalog: 
NCBI Published Medical (?)
PMID: 16515776

Turabian/Chicago Citation

Hong Mu, Ryuji Ohashi, Shaoyu Yan, Hong Chai, Hui Yang, Peter Lin, Qizhi Yao and Changyi Chen. Apr 1, 2006. "Adipokine resistin promotes in vitro angiogenesis of human endothelial cells." Cardiovascular Research 70: 1: 146-157. 10.1016/j.cardiores.2006.01.015.

Wikipedia Citation

<ref> {{Cite journal | doi = 10.1016/j.cardiores.2006.01.015 | issn = 0008-6363 | volume = 70 | pages = 146-157 | last = Mu | first = Hong | coauthors = Ohashi, Ryuji, Yan, Shaoyu, Chai, Hong, Yang, Hui, Lin, Peter, Yao, Qizhi, Chen, Changyi | title = Adipokine resistin promotes in vitro angiogenesis of human endothelial cells | journal = Cardiovascular Research | date = Apr 1, 2006 | pmid = | pmc = }} </ref>