TY - JOUR AB - The proliferation and migration of vascular smooth muscle cells (SMCs) play critical roles in intimal thickening and neointimal hyperplasia in early-phase atherosclerosis. This study tested whether wild grape extract (WGE) suppressed the proliferation and migration of human aortic SMCs induced by neighboring macrophages. Cellular expression of fibrogenic connective tissue growth factor (CTGF) and secretion of collagen IV and matrix metalloproteinase (MMP)-2 were determined in SMCs exposed to THP-1-differentiated macrophage-conditioned media. Proliferation was enhanced in SMCs exposed to macrophage-conditioned media collected during the early stage of differentiation, which was attenuated by treatment with ≥10 µg/ml WGE. Increased secretion of CTGF and collagen IV macrophage-conditioned media was suppressed in WGE-supplemented SMCs. TGF-β1-promoted production of CTGF and collagen IV was suppressed by blocking TGF-β receptors of R1 and R2 in SMCs. WGE repressed macrophage-conditioned media-upregulated MMP-2 secretion, indicating that WGE had an ability to encumber plaque rupture within atherosclerotic lesions. In addition, ≥1 µg/ml WGE ameliorated the migration of SMCs promoted by neighboring macrophages. These results demonstrate that WGE retarded neointimal hyperplasia and thickening within atherosclerotic plaques largely comprising of macrophages and SMCs. Therefore, WGE may be developed as an anti-proliferative and anti-migratory agent targeting SMCs in the proximity of newly differentiated and resident macrophages. AD - Department of Food and Nutrition, Hallym University, Chuncheon, Republic of Korea Chuncheon Bioindustry Foundation, Chuncheon, Republic of Korea AU - Kang,Sang-Wook AU - Kim,Min ,Soo AU - Kim,Hyun-Sung AU - Lee,Yong-Jin AU - Kang,Young-Hee DA - 2012/06/01 DO - 10.3892/ijmm.2012.931 EP - 1145 IS - 6 JO - Int J Mol Med KW - collagen IV connective tissue growth factor macrophages smooth muscle cell migration wild grape extract PY - 2012 SN - 1107-3756 1791-244X SP - 1137 ST - Anti-atherogenic activity of wild grape (Vitis thunbergii) extract antagonizing smooth muscle cell proliferation and migration promoted by neighboring macrophages T2 - International Journal of Molecular Medicine TI - Anti-atherogenic activity of wild grape (Vitis thunbergii) extract antagonizing smooth muscle cell proliferation and migration promoted by neighboring macrophages UR - https://doi.org/10.3892/ijmm.2012.931 VL - 29 ER -