Soluble CD40 ligand induces human coronary artery smooth muscle cells proliferation and migration

Background. Clinical data have shown that an increased level of serum soluble CD40 ligand (sCD40L) is associated with atherosclerogenesis. We hypothesize that sCD40L induces proliferation and migration of vascular smooth muscle cells, (VSMCs) through activation of matrix metalloproteinases (MMPs). Methods. Human VSMCs were treated with sCD40L (1 or 5 mu g/mL). Cell proliferation, and migration, were studied using a nonradioactive cell proliferation assay (MTT) and a modified Boyden chamber combined it with a scrape-wound assay, respectively. Messenger RNA (mRNA) and protein levels of MMP-2 and MMP-9 were measured with real-time polymerase chain reaction and, enzyme-linked immunosorbent assays. Neutralizing antibodies against MMP-2 or MMP-9 were used to evaluate their effects on sCD40L-induced cell proliferation, and migration. Results. MTT assay) showed a 35% increase in cell proliferation in the high-dose (5 mu g/mL) sCD40L-treated group. Cell migration was also increased by 33% (Transwell assay) to 3-fold (scrape-wound assay) after high-dose sCD40L treatment. When cells were treated with. 5 mu g/mL of sCD40L fiar 24 hours, significant decreases in MMP-2 and increases in MMP-9 mRNA and protein levels were observed. Neutralizing antibodies against, MMP-9 effectively blocked sCD40L-induced cell proliferation and migration. Conclusion. This study suggests that sCD40L increases VSMC proliferation and migration through the MMP-9 pathway, which may be a potential mehanism through which sCD40L induces intimal hyperplasia and atherosclerosis. (Surgery 2009;146:5-11.)