Posted on

Differential Leukocyte and Endothelial Responses through VEGFR1 and VEGFR2

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, VEGF120(121) and VEGF164(165), was studied in the transparent and avascular adult mouse cornea.

Methods: Controlled-release pellets containing equimolar amounts of VEGF120 and VEGF164 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: VEGF164 was found to be significantly more potent at inducing inflammation. In vivo blockade of VEGF receptor (VEGFR)-1 significantly suppressed VEGF164-induced corneal inflammation. In vitro, VEGF165 more potently stimulated intracellular adhesion molecule (ICAM)-1 expression on endothelial cells, an effect that was mediated by VEGFR2. VEGF164 was also more potent at inducing the chemotaxis of monocytes, an effect that was mediated by VEGFR1. In an immortalized human leukocyte cell line, VEGF165 was found to induce tyrosine phosphorylation of VEGFR1 more efficiently.

conclusions. Taken together, these data identify VEGF164(165) as a proinflammatory isoform and identify multiple mechanisms underlying its proinflammatory biology.

http://www.iovs.org/content/45/2/368.long

Posted on

NADPH oxidase activity is required for endothelial cell proliferation and migration

NADPH oxidase has been shown to play an important role in cardiovascular biology. The goal of the present study was to determine whether NADPH oxidase activity is important for endothelial cell growth and migration. In proliferation assays, growth factor- or serum-induced DNA synthesis in three different types of human endothelial cells was abrogated by inhibitors of NADPH oxidase, but not by inhibitors of xanthine oxidase or nitric oxide synthase. Moreover, vascular endothelial growth factor-induced migration of human endothelial cells was suppressed in the presence of NADPH oxidase inhibitors. These results support a potential role for NADPH oxidase in mediating angiogenesis.

full text by subscription at:

http://linkinghub.elsevier.com/retrieve/pii/S0014-5793%2800%2902305-X