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-kappaB 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 not with U0126, suggesting the crucial role of PI3Kinase and NF-kappaB 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-kappaB 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.