MONOCYTE CHEMOATTRACTANT PROTEIN-1 INHIBITS GROWTH OF RAT VASCULAR SMOOTH-MUSCLE CELLS

The early atherosclerotic lesion is characterized by the migration of inflammatory cells, including monocytes, which may serve as a source of cytokines such as monocyte chemoattractant protein 1 (MCP-1), a homologue of mouse JE. We investigated the effect of MCP-1 on the growth of vascular smooth muscle cells (VSMC) isolated from rat aortae. In Northern blot analysis, MCP-1/JE transcripts were not observed in unstimulated VSMC, but its expression was clearly observed by exposure to lipopolysaccharide (1 mu g/ml) for 6 h. Human recombinant MCP-1 inhibited the uptake of [H-3]thymidine by VSMC cultured in 0.5% fetal bovine serum (FBS) containing Dulbecco's modified Eagle's medium (DMEM) in a dose-dependent manner. The inhibitory effect of MCP-1 on the growth of VSMC was also confirmed by a change in cell counts. The antiproliferative effect of MCP-1 was significantly blocked in the presence of an anti-MCP-1 antibody. MCP-1-induced inhibition of [H-3]thymidine uptake was not affected in the presence of indomethacin (1 mu g/ml) or N-G-monomethyl-L-arginine (0.1 mM), and MCP-1 showed no effect on 6-ketoprostaglandin F-1 alpha, guanosine 3',5'-cyclic monophosphate, and adenosine 3',5'-cyclic monophosphate syntheses in VSMC. These results indicate that MCP-1 inhibits the proliferation of VSMC in vitro and that its effect is independent of prostaglandin or nitric oxide generation.