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VEGF(164(165)) as the pathological isoform: Differential leukocyte and endothelial responses through VEGFR1 and VEGFR2

Biomedical Sciences Research Institute Computer Science Research Institute Environmental Sciences Research Institute Nanotechnology & Advanced Materials Research Institute

Usui, T, Isbida, S, Yamasbiro, K, Kaji, Y, Poulaki, V, Moore, Johnny, Moore, Tara, Shima, DT and Adamis, AP (2004) VEGF(164(165)) as the pathological isoform: Differential leukocyte and endothelial responses through VEGFR1 and VEGFR2. INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE, 45 (2). pp. 368-374. [Journal article]

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DOI: 10.1167/iovs.03-0106

Abstract

PURPOSE. Vascular endothelial growth factor (VEGF) induces angiogenesis and vascular permeability and is thought to be operative in several ocular vascular diseases. The VEGF isoforms are highly conserved among species; however, little is known about their differential biological functions in adult tissue. In the current study, the inflammatory potential of two prevalent VEGF isoform splice variants, WGF(120(121)) and VEGF(164(165)), was studied in the transparent and avascular adult mouse cornea. METHODS. Controlled-release pellets containing equimolar amounts of VEGF(120) and VEGF(164) were implanted in corneas. The mechanisms underlying this differential response of VEGF isoforms were explored. The response of VEGF in cultured endothelial cells was determined by Western blot analysis. The response of VEGF isoforms in leukocytes was also investigated. RESULTS. VEGF(164) was found to be significantly more potent at inducing inflammation. In vivo blockade of VEGF receptor (VEGFR)-1 significantly suppressed VEGF(164)-induced corneal inflammation. In vitro, VEGF(165) more potently stimulated intracellular adhesion molecule (ICAM)-1expression on endothelial cells, an effect that was mediated by VEGFR2. VEGF(164) was also more potent at inducing the chemotaxis of monocytes, an effect that was mediated by VEGFR1. In an immortalized human leukocyte cell line, VEGF(165) was found to induce tyrosine phosphorylation of VEGFR1 more efficiently. CONCLUSIONS. Taken together, these data identify VEGF(164(165)) as a proinflammatory isoform. and identify multiple mechanisms underlying its proinflammatory biology.

Item Type:Journal article
Faculties and Schools:Faculty of Life and Health Sciences
Faculty of Life and Health Sciences > School of Biomedical Sciences
Research Institutes and Groups:Biomedical Sciences Research Institute
Biomedical Sciences Research Institute > Vision
ID Code:3518
Deposited By:Professor Tara Moore
Deposited On:18 Dec 2009 14:45
Last Modified:20 Feb 2014 11:15

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