Advanced glycation endproducts stimulate mitogen-activated protein kinase and proliferation in rabbit vascular smooth muscle cells

Advanced glycation end products of bovine serum albumin (AGEs-BSA) exhibited biphasic effects on the proliferation of cultured rabbit vascular smooth muscle cells (VSMCs) in terms of [³H]thymidine incorporation and cell number count; a stimulatory effect was observed at 1-10 μg/ml and an inhibitory effect at more than 20 μg/ml, while it inhibited [³H]thymidine incorporation even at 1-10 μg/ml in cultured bovine vascular endothelial cells (VECs). Transient activation of p42 mitogen-activated protein kinase (MAPK) with a peak at around 5 min and a subsequent sustained phase was induced by AGEs-BSA in VSMCs, but not in VECs. The dependence of MAPK activation on AGEs-BSA dose was correlated with that of VSMCs proliferation.