The Library
Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways : novel insights into visfatin-induced angiogenesis
Tools
Tools
Tools
Adya, Raghu, Tan, Bee K., Punn, Anu, Chen, Jing and Randeva, Harpal S. (2008) Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways : novel insights into visfatin-induced angiogenesis. Cardiovascular Research, Vol.78 (No.2). pp. 356-365. doi:10.1093/cvr/cvm111 ISSN 0008-6363.
Research output not available from this repository.
Request-a-Copy directly from author or use local Library Get it For Me service.
Official URL: http://dx.doi.org/10.1093/cvr/cvm111
Abstract
AIMS: Visfatin is a novel adipokine whose plasma concentrations are altered in obesity and obesity-related disorders; these states are associated with an increased incidence of cardiovascular disease. We therefore investigated the effect of visfatin on vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP-2, MMP-9) production and the potential signalling cascades.
METHODS AND RESULTS: In human umbilical vein endothelial cells (HUVECs), visfatin significantly and dose-dependently up-regulated gene expression and protein production of VEGF and MMPS and down-regulated expression of tissue inhibitors of MMPs (TIMP-1 and TIMP-2). The gelatinolytic activity of MMPs (analysed by zymography) correlated with mRNA and western blot findings. Interestingly, visfatin significantly up-regulated VEGF receptor 2 expression. Inhibition of VEGFR2 and VEGF [by soluble FMS-like tyrosine kinase-1 (sFlt1)] down-regulated visfatin-induced MMP induction. Visfatin induced dose-and time-dependent proliferation and capillary-like tube formation. Importantly, visfatin was noted to have anti-apoptotic effects. In HUVECs, visfatin dose-dependently activated PI3K/Akt (phosphatidylinositol 3-kinase/Akt) and ERK1/2 (extracellular signal-regulated kinase) pathways. The functional effects and MMP/VEGF induction were shown to be dependent on the MAPK/PI3K-Akt/VEGF signalling pathways. Inhibition of PI3K/Akt and ERK1/2 pathways led to significant decrease of visfatin-induced MMP and VEGF production and activation, along with significant reduction in endothelial proliferation and capillary tube formation.
CONCLUSION: Our data provide the first evidence of visfatin-induced endothelial VEGF and AAMP production and activity. Further, we show for the first time the involvement of the MAPK and PI3K/Akt signalling pathways in mediating these actions, as welt as endothelial cell proliferation. Collectively, our findings provide novel insights into visfatin-induced endothelial angiogenesis.
| Item Type: | Journal Article | ||||
|---|---|---|---|---|---|
| Subjects: | Q Science > QP Physiology R Medicine > RC Internal medicine |
||||
| Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Translational & Experimental Medicine > Metabolic and Vascular Health (- until July 2016) Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School |
||||
| Library of Congress Subject Headings (LCSH): | Vascular endothelial growth factors, Metalloproteinases , Neovascularization, Cardiovascular system -- Diseases -- Research | ||||
| Journal or Publication Title: | Cardiovascular Research | ||||
| Publisher: | Oxford University Press | ||||
| ISSN: | 0008-6363 | ||||
| Official Date: | 1 May 2008 | ||||
| Dates: |
|
||||
| Volume: | Vol.78 | ||||
| Number: | No.2 | ||||
| Number of Pages: | 10 | ||||
| Page Range: | pp. 356-365 | ||||
| DOI: | 10.1093/cvr/cvm111 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Restricted or Subscription Access | ||||
| Funder: | General Charities of the City of Coventry |
Data sourced from Thomson Reuters' Web of Knowledge
Request changes or add full text files to a record
Repository staff actions (login required)
 |
View Item |
