E. Porreca et al., MONOCYTE CHEMOTACTIC PROTEIN-1 (MCP-1) IS A MITOGEN FOR CULTURED RAT VASCULAR SMOOTH-MUSCLE CELLS, Journal of vascular research, 34(1), 1997, pp. 58-65
The involvement of inflammatory mechanisms in the progression of ather
osclerosis has recently been suggested. Monocyte chemotactic protein 1
(MCP-1) is a soluble protein which is implicated in acute and chronic
inflammatory processes, including atherosclerosis. We evaluated the e
ffect of human recombinant MCP-1 on the in vitro proliferation of rat
vascular smooth muscle cells (VSMCs), Incubation of VSMCs with MCP-1 (
50-200 ng/ml) in the presence of 0.5% FCS significantly increased cell
proliferation, [H-3]-thymidine incorporation and the proliferative S
fraction, measured by flow cytometry, compared to control cells. The p
roliferative effect of MCP-1 was specific, as shown by inhibition with
a rabbit polyclonal serum to MCP-1, Moreover, the mitogenic effect of
MCP-1 was significantly inhibited by downregulation of protein kinase
C (PKC) activity and by incubation with H-7, a protein kinase inhibit
or, suggesting the involvement of the PKC system. Verapamil, a Ca2+ ch
annel blocker, also reduced the stimulatory effect of MCP-1 on cell pr
oliferation. This study demonstrates that MCP-1 does not merely have a
chemotactic activity, but also a mitogenic effect on cultured rat VSM
Cs.