MicroRNA-155Inhibitor Alleviates Activated CD4+T Cell Induced Endothelial Cell Inflammtory Reaction And Smooth Muscle Cell Proliferation

OBJECTIVE—Several clinical studies have shown the decrease of MicroRNA-155inperipheral blood in the patients with atherosclerosis, and MicroRNA-155has beenidentified as an important opponent in the process of lymphocyte activation. Usinglentivirus containing microRNA-155inhibitor to transfect human na ve CD4+T cell, weexamined the ability of microRNA-155inhibitor to alter the balance between T cellsubsets and cytokine secretion profile plus the influence on endothelial cell inflammatoryreaction and smooth muscle cell proliferation.RESEARCH DESIGN AND METHODS—Naive CD4+T cell isolated from umbilicalblood were transfected with lentivirus containing microRNA-155inhibitor sequence or thecontrol virus and stimulated by oxLDL-specific dendritic cell, and then evaluate theproliferation, differentiation and cytokine secretion profile of mature CD4+T cell.3daysafter the mature CD4+T cell were added to the vascular model constituted of humanumbilical vein endothelial cell and smooth muscle cell, the inflammatory reaction plusapotosis of endothelial cell and smooth muscle cell proliferation were tested.RESULTS—During3days after transfection, microRNA-155inhibitor sequencesignificantly depressed proliferation, changed the balance of T cell subsets to Th2and Treg,altered cytokine secretion profile to vascular proctive aspect, alleviated lymphocyteadhesion compared with the groups of wide-type and that transfected with control virus.Moreover, the vascular model cocultured with microRNA-155inhibitor sequencetransfected T cell shows dampened endothelial cell inflammtory reaction, both adhesionmolecules,NF-κB pathway and apotosis, and alleviated smoothe muscle cell proliferation,such as nucleotide uptake, cell cycle, Wnt pathway and healing assay.CONCLUSIONS—These findings identify microRNA-155as a novel target for the prevention of endothelial cell dysfunction plus apoptosis and smooth muscle cellproliferation occurring in atherosclerosis via influence on lymphocyte proliferation anddifferntiation.