Objective - We investigated the role of monocyte chemoattractant protein-1 (MCP-1) in vascular endothelial growth factor (VEGF)-induced angiogenesis and vascular permeability and the underlying molecular mechanism of VEGF-induced endothelial MCP-1 expression in vitro and in vivo. Methods and Results - We used an anti-MCP-1 neutralizing antibody for specific inhibition of MCP-1. VEGF increased tubule formation in the angiogenesis assay and vascular permeability in the Miles assay, and these effects were markedly inhibited by anti-MCP-1 antibody. Using a luciferase MCP-1 promoter-gene assay, we found that the activator protein-1 (AP-1) binding site of the MCP-1 promoter region contributes to the increase in MCP-1 promoter activity by VEGF. To specifically inhibit AP-1, we used recombinant adenovirus containing a dominant-negative c-Jun (Ad-DN-c-Jun). Ad-DN-c-Jun inhibited VEGF-induced endothelial MCP-1 mRNA expression and promoter activity in vitro. In vivo gene transfer of DN-c-Jun into rat carotid artery, with the hemagglutinating virus of the Japan liposome method, significantly blocked VEGF-induced MCP-1 and macrophage/monocyte (ED1) expression in endothelium. Conclusions - These results reveal that endothelial MCP-1 induced by VEGF seems to participate in angiogenesis, vascular leakage, or arteriosclerosis. AP-1 plays a critical role in the molecular mechanism underlying induction of MCP-1 by VEGF.
|Number of pages||6|
|Journal||Arteriosclerosis, thrombosis, and vascular biology|
|Publication status||Published - Nov 1 2003|
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine