SDF-1Promotes Ox-LDL Induced Vascular Smooth Muscle Cell Proliferation

PurposeInvestigate the mechanism of the regulatory roles of Stromal cell derived factor-1(SDF-1)/C-X-C motif receptor4(CXCR4) on cell proliferation and apoptosis invascular smooth muscle cells (VSMC) via the Protein kinase C (PKC) and nuclearfactor-kappaB (NF-κB) signaling pathways.MethedApplication of immune histochemical method detected the expression ofatherosclerotic lesions in the SDF-1receptor Rat aortic VSMC were treated withcontrol, or oxidized low-density lipoprotein (ox-LDL); Atherosclerosis (AS) model.Cells exposed to the AS model were then treated with SDF-1, plus inhibitors specificfor PKC (Ro31-8220), CXCR4(12G5), or NF-κB (pyrrolidine dithiocarbamate, PDTC).The rate of cell proliferation was detected using MTT assay, while the rate of apoptosiswas measured using flow cytometry. NF-kB protein expression was analyzed usingwestern blot..Result1. CXCR4, the only receptor of SDF-1, was shown to be highly expressed inatherosclerotic plaques.2. The proliferation rate in the AS model group was significantly higher comparedwith control group, but lower than the SDF-1group (p <0.05). There was nosignificance difference in the Ro31-8220,12G5and PDTC groups when compared withAS model group (p>0.05). The apoptosis rate in the AS model group (ox-LDL) wassignificantly higher than the normal control group (p <0.05). In addition, the apoptosisrate in the SDF-1group was significantly lower than the normal control group (p<0.05); however, there was no difference when compared with the Ro31-8220group.The expression level of NF-κB protein in the SDF-1treated group was significantlyhigher than the AS model (ox-LDL) group (p <0.05), but there was no significantdifference when compared with the Ro31-8220group (p>0.05). Conclusion1. CXCR4is confirmed to be actively expressed in atherosclerotic lesions,but it israrely expressed in normal arterial walls.2. SDF-1can increase significantly proliferation of VSMC induced by ox-LDLthrough SDF-1/CXCR4axis.3. SDF-1can reduced significantly the number of apoptotic of VSMC induced byox-LDL through SDF-1/CXCR4axis.4. SDF-1can increase significantly proliferation of VSMC and reduced thenumber of apoptotic of VSMC induced by ox-LDL,and these effect is throughSDF-1/CXCR4axis,but blocking CXCR4and NF-κB can completely inhibit SDF-1toinfluence the growth in VSMC.Howere, this effect is not fully regulated by PKC.Further investigations are needed to determine the exact mechanism in regulation.