Atherosclerosis and post-angioplasty restenosis are characterized by the abnormal activation of vascular smooth muscle cell (VSMC) and inflammatory cells, and the excessive accumulation of extracellular matrix (ECM) proteins. In general, VSMC which is...
Atherosclerosis and post-angioplasty restenosis are characterized by the abnormal activation of vascular smooth muscle cell (VSMC) and inflammatory cells, and the excessive accumulation of extracellular matrix (ECM) proteins. In general, VSMC which is a contractile form maintains the blood vessel, but VSMC is transformed into a synthetic form by blood. When vascular endothelial cell is injured, VSMC is activated via contacting with growth factors and ECM proteins. The activation of VSMC causes the neointimal hyperplasia and finally interferes blood flow. In this study, we treated curcumin, an anti-oxidant and anti-inflammatory compounds, isolated from the root of the plant Curcuma longa L. to rat aortic smooth muscle cells (RAoSMCs) to investigate its anti-proliferative mechanism. Cytoskeletal change of RAoSMC treated with curcumin was characterized by α-tubulin staining and cell signaling changes were also investigated by western blotting and RT-PCR analysis. Apoptosis of the cells treated with curcumin was demonstrated by DNA laddering analysis. Also, protein changes of curcumin-treated RAoSMC were determined by 2-D electrophoresis, in-gel digestion, MALDI-TOF MS, and proteome bioinformatics analysis. These results showed that curcumin inhibited serum- and PDGF-stimulated proliferation of RAoSMCs in a dose-dependent manner, by arresting G0G1 phase of cell cycle and inducing apoptosis. Also the mRNA level of c-myc in PDGF-stimulated RAoSMCs was significantly reduced, and cytoskeleton was not changed in spite of cell shrinkage. Proteomics studies revealed that enzymes which is participated in metabolism were reduced and heat shock protein or stress protein were increased. These results suggest that the effect and inhibitory mechanism of curcumin on vascular smooth muscle cells are due to specific inhibition of the PDGF-signaling pathway, cell cycles, and activation of apoptosis. Also, we have tested the biological effects of curcumin-diglucoside (CDG) which is a soluble derivative of curcumin on SMC.