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Pre-B cell colony enhancing factor (PBEF)/visfatin induces secretion of MCP-1 in human endothelial cells : role in visfatin-induced angiogenesis

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Adya, Raghu, Tan, Bee K., Chen, Jing and Randeva, Harpal S.. (2009) Pre-B cell colony enhancing factor (PBEF)/visfatin induces secretion of MCP-1 in human endothelial cells : role in visfatin-induced angiogenesis. Atherosclerosis, Vol.205 (No.1). pp. 113-119. ISSN 0021-9150

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Official URL: http://dx.doi.org/10.1016/j.atherosclerosis.2008.1...

Abstract

Objectives: Visfatin and Monocyte-Chemoattractant-Protein-1 (MCP-1) are elevated in cardiovascular pathologies, insulin-resistant and diabetic states. Visfatin has been reported to exhibit pro-angiogenic actions in human endothelial cells. Given MCP-1's well described pro-angiogenic properties we sought to study the potential interaction between visfatin and MCP-1 in human endothelial cells. We also explored the possible autocrine/paracrine mechanisms governing this potential interaction; specifically we looked at the effect of visfatin on MCP-1's putative receptor (CCR2 receptor) in human endothelial cells. Methods and results: Using in vitro angiogenic assays (capillary tube formation and migration), Western blotting and RT-PCR, we found that visfatin, dose-dependently, induced MCP-1 as well as CCR2 levels. We also studied the involvement of PI3Kinase, MAPKinase and NF-kappa B pathways in visfatin induced MCP-1/CCR2 levels by employing LY294002, U0126 and BAY11-7085, respectively. We found the increase in MCP-1 and CCR2 levels by visfatin were negated by LY294002 and BAY11-7085, but notwith U0126, suggesting the crucial role of PI3Kinase and NF-kappa B pathways in visfatin induced MCP-1 and its autocrine regulation via the CCR2 receptor. Finally, we consolidate the role of MCP-1 in visfatin-induced angiogenesis by employing CCR2 antagonist (RS-102895) and MCP-1 neutralising antibody, respectively. Conclusions: Our novel data reveal that MCP-1 is pivotal in modulating visfatin-induced angiogenesis via NF-kappa B and PI3Kinase pathways. Furthermore, our findings elucidate the potential influence of autocrine/paracrine mechanisms (via the CCR2 receptor) underlying visfatin's angiogenic effects through MCP-1. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Item Type: Journal Article
Subjects: R Medicine > RC Internal medicine
Divisions: Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health
Faculty of Medicine > Warwick Medical School
Journal or Publication Title: Atherosclerosis
Publisher: Elsevier Ireland Ltd.
ISSN: 0021-9150
Date: July 2009
Volume: Vol.205
Number: No.1
Number of Pages: 7
Page Range: pp. 113-119
Identification Number: 10.1016/j.atherosclerosis.2008.11.024
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access
Funder: University of Warwick
URI: http://wrap.warwick.ac.uk/id/eprint/27624

Data sourced from Thomson Reuters' Web of Knowledge

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