Cyclic stretch (CS) mediates different cellular functions in vascular smooth muscle cells and involves in neointimal hyperplasia and subsequent atherosclerosis of vein grafts. Here, we investigated whether CS can modulate stromal cell-derived factor-1 alpha (SDF-1 alpha)/CXCR4 axis in human saphenous vein smooth muscle cells. We found CS induced the upregulation of SDF-1 alpha and CXCR4 in human saphenous vein smooth muscle cells in vitro, which was dependent on P13K/Akt/mTOR pathway. Furthermore, CS augmented human saphenous vein smooth muscle migration and focal adhesion kinase (FAK) activation by P13K/Akt/mTOR pathway. Interestingly, the upregulation of SDF-1 alpha/CXCR4 axis was instrumental in CS-induced saphenous vein smooth muscle cell migration and FAK activation, as showed by AMD3100, an inhibitor of SDF-1 alpha/CXCR4 axis, partially but significantly blocked the CS-induced cellular effects. Thus, those data suggested SDF-1 alpha/CXCR4 axis involves in CS-mediated cellular functions in human saphenous vein smooth muscle cells. (C) 2009 Elsevier Inc. All rights reserved.