Differential Modulation of Cytokines by VEGF In End Stage Renal Disease

Abstract 5187

Vascular endothelial growth factor (VEGF) mediates nitric oxide dependent angiogenic effects contribute to the inflammatory responses. VEGF is upregulated in ESRD and contributes to the cardiovascular dysfunction in ESRD. VEGF is also upregulated by erythropoietin which is commonly used in the management of ESRD patients. With the availability of BioChip Array Technology, a multiparametric screening of inflammatory mediators/cytokines can be measured and relevance of VEGF can be established. Utilizing the Randox Biochip technology, we profiled the plasma samples from 53 ESRD patients to determine their relevance to VEGF levels. Pre-dialysis samples from 53 male and female ESRD patients on maintenance hemodialysis were analyzed using a cytokine biochip for VEGF, IL2, IL4, IL6, IL8, IFNG1, TNF, IL1, MCP-1 and EGF. In addition, NO, asymmetric dimethyl arginine (ADMA), serotonin and functional microparticles levels were also measured. A group of 50 normal healthy males and females constituted the control group. The circulating levels of VEFG and mediators were compared with the normals. In addition, VEGF levels were compared with the other mediators. In comparison to the normals, ESRD patients exhibited decreased levels of IL4, IL8, TNF and EGF, which ranged from 20–210%. Increased levels of IL2, IL6, IL10, IFNG1, IL1 and MCP-1 were noted (20-350%). NO levels were also increased, however ADMA remained unchanged. Both the serotonin and microparticle levels were also elevated in comparison to the normals (p>0.05) VEGF levels showed wide variation, however on a cumulative basis a 30–210% increase in VEGF was noted. Except for the MCP-1, the correlation of VEGF with other inflammatory markers was relatively poor (r²=<0.25). These results show that ESRD patients can be profiled for various inflammatory mediators. VEGF levels were markedly increased, however only MCP-1 levels correlated well with the increase in VEGF levels. Additional studies are warranted to clarify the regulatory role of VEGF and other mediators on inflammatory cytokines and cellular activation in ESRD.