Abstract:Aim To evaluate the effect of cariporide on the proliferation of rat aortic smooth muscle cells (VSMC) induced by advanced glycation end products (AGE). Methods The cultured vascular smooth muscle cells of rat (VSMC) were exposed to normal Dulbecco's Modified Eagle Medium (DMEM) or AGEs-supplemented DMEM for 24 hours in the presence or absence of cariporide. Proliferations of cells were observed by MTT colorimetric assay and determination of total protein level in cells. Intracellular pH and free Ca2+ concentration ([Ca2+] i) were measured by using the pH-sensitive fluorescent dye BCECF and the Fura-2 technique respectivelly. Results AGEs significantly increased the VSMC MTT light absorption (0.554±0.032 vs 0.155±0.018) and total protein level compared with the control group(193.3±10.7 μmol/L vs 127.8±8.2 μmol/L, P<0.01); cariporide significantly inhibited these effects induced by AGEs in a concentration-dependent manner. Cariporide 0.1, 1, 10 μmol/L reduced the MTT light absorption, from 0.554±0.032 to 0.402±0.028, 0.298±0.020, 0.174±0.019 while the total protein level of cells from (193.3±10.7) μmol/L to (180.9±9.8) μmol/L, (156.4±9.4) μmol/L, (130.6±8.8) μmol/L respectively. Moreover, cariporide simultaneously reduced the intracellular pH and Ca2+concentration. Conclusion AGE can significantly promote the VSMCs proliferation; cariporide can inhibit the VSMC proliferation induced by AGEs, the mechanism involves reducing the pHi and [Ca2+] i.