Inhibition of glutathione on vascular smooth muscle cell proliferation mediate by advanced glycation end products

Background To confirm the proliferation of vascular smooth muscle cell （VSMC） lead by advanced glycation end products （AGEs） and investigate weather the mechanism is work through MAPK pathway. To investigate weather the prolification of VSMC lead by AGEs can be inhibited by reduced glutathione（GSH） and what the mechanisam is. Methods VSMC of rats were isolated and cultivated, separated in 8 groups, each group contained 12 samples. Density of cell was 1×105 /mL in each sample, cultivated with AGEs at different concentrations and intervened with GSH at different concentrations. In order to determine the mechanism and interventional factors of VSMCs, sandwich ELISA method was used to test the concentration of P-P38 and MTT colorimetry was adopted to evaluate the amount of VSMC. Results 1.Effect of AGEs to the OD value of MTT in VSMC： with stimulation of AGEs, OD valued of P-P38 in VSMC increased simultaneously （P0.01）, their value were 0.43±0.15, 0.49±0.16, 0.48±0.19 [L/（g·cm）]. With the increase of the dose of AGEs, there were no difference between groups B, C of MTT OD value（P0.05）. 2.Effect of GSH to the OD value of MTT in VSMC stimulated by AGEs： OD value of MTT decreased with the increase of GSH concentration, their value were 0.347±0.102, 0.333±0.108, 0.285±0.080 [L/（g·cm）] respectively, decreased by 45%, 56%, 60%（P0.01）compared with value of AGEs control group. With the increasing of the dose of GSH, the MTT OD value had no difference between groups F, G and H （P0.05）. 3.Effect of AGEs to the OD value of P-P38 in VSMC： with stimulation of AGEs, OD valued of P-P38 in VSMC increased obviously （P0.01）, their value were 0.65±0.17, 0.85±0.26, 0.94±0.17 [L/（g·cm）]. With the increasing of the dose of AGEs, the P-P38 OD value increase simultaneously（P0.05）. 4.Effect of GSH on the OD value of P-P38 in VSMC stimulated by AGEs： OD value of P-P38 decreased with the increasing of GSH concentration, their value were 0.356±0.090, 0.281±0.070, 0.256±0.072 [L/（g·cm）] respectively, decreased by 45%, 56%, 60%（P0.01）compared with the value of control group. With the increasing of the dose of GSH, the P-P38 OD value between groups F, G and H were decreased gradually （P0.01）. Conclusions 1.AGEs has the function of inducing the proliferation of vascular SMC, the activation of the P-P38 MAPK signal pathway may be the mechanism of the proliferation of VSMC. 2.GSH can inhibit the proliferation of VSMC lead by AGEs, The P-P38-MAPK pathway is being blocked by GSH, which is the mechanism of inhibiting the proliferation of VSMC lead by AGEs.

Glycyrrhizic Acid Attenuates Balloon-Induced Vascular Injury Through Inactivation of RAGE Signaling Pathways

Percutaneous coronary intervention is a well-established technique used to treat coronary artery disease,but the risk of coronary artery in-stent restenosis following percutaneous coronary intervention is still high.Previous studies revealed that high mobility group protein B1(HMGB1)plays a critical role in neointima formation.In this study,we aimed to investigate the role of glycyrrhizic acid(GA),an HMGB1 inhibitor,in the process of neointima formation and the potential mechanisms.We investigated the role of GA in neointima formation through an iliac artery balloon injury model in rabbits.Proliferation,migration,and phenotype transformation of human vascular smooth muscle cells(VSMCs)were observed.Besides,infl ammation and receptor for advanced glycosylation end products(RAGE)signaling pathways were studied.The results indicate that GA attenuated neointima formation and downregulated HMGB1 expression in injured artery in rabbits.HMGB1 promoted proliferation,migration,and phenotype transformation through the activation of RAGE signaling pathways in VSMCs,and blockade of HMGB1 by GA(1,10,and 100μM)could attenuate those processes and reduce proliferation of human VSMCs.In conclusion,the HMGB1 inhibitor GA might be useful to treat proliferative vascular diseases by downregulating RAGE signaling pathways.Our results indicate a new and promising therapeutic agent for restenosis.