Antiatherosclerosis Induced By Ligustrazine Targeting Endothelium

Objective:1. To examine the antiatherosclerotic efficacy induced by LIG and its underlying mechanisms.2. To widen its clinical usage scope, to provide sensitive markers for clinical diagnose in the earlier time of atherosclerosis. Methods:1. In in vivo experiments, rabbits fed by high cholesterol diet have been used to evaluate the antiatherosclerotic efficacy of LIG (75,150mg.kg-1) including plaque surface area in aorta, I/M, foam cell amounts, serum lipid level of TC,TG,LDL-C and HDL-C.2. Further investigation had been carried out in in vitro experiments induced by ox-LDL in HCAEC through examining the effects of LIG on the gene and protein expression of MCP-1, ICAM-1, COX-2 and their common related signal pathways such as NF-κB.3. A proteomic analysis of LIG against ox-LDL-induced HCAEC was performed. The differentially expressed proteins induced by LIG were identified by using LC-ESI-MS/MS, the SWISS-PROT database and KEGG signals forecast. Further function validation of these pathways and targets in endothelial cells were carried out. Results:1. LIG could reduce the plaque surface area in aorta at the dose of 75 and 150mg.kg-1. I/M and foam cell amounts were also decreased. In addition, serum lipid level of TC,TG and LDL had been depressed, however serum level of HDL had no changes.2. LIG markedly decreased the gene and protein expression of MCP-1, ICAM-1 and COX-2 at the concentration of 1,10 and 100μM. The translocation of NF-κB to nuclear had been restrained.3. Twelve of approximately 400 detected proteins were either increased or decreased in abundance as a result of treatment with LIG. Among them,9 spots were more than 2-fold up-regulated and 3 were more than 2-fold down-regulated by LIG compared with ox-LDL-treated samples, identified by comparing masses of their tryptic peptides with those of known proteins, using LC-ESI-MS/MS and the SWISS-PROT database.Their functions have been annotated in Expasy databases including lipid and energy metabolism, chaperone, receptor tyrosine kinases, cytoskeleton regulation and ubiquitin-proteasome system (UPS). Conclusion:1. Antiatherosclerotic effects induced by LIG are targeting endothelial cells. 2. One of the the characteristics of LIG is that multitargets in endothelial cells have been involved in its underlying mechanisms against atherosclerosis.