The Role Of Ras-Rho Kinase Signaling Pathway And PPARs On Regulation Of Vecs Of CX 43

[Objective] To investigate the Ras-Rho signal pathway inhibitors (farnesylthiosalicylic acid, FTS) with a PPAR gamma agonist rosiglitazone and antagonist GW9662 in the regulation of vascular endothelial cell gap junction protein 43 (connexin 43, Cx 43) expression on mechanism and its possible relationship, so as to find the mechanism of atherosclerosis and the possible relationship.[Methods] Cultured human coronary artery endothelial cells (HCMEC), use the MTT method for detection of different concentration gradient, i.e.0.1,1,10, 25,50ug/mL LPS and different time gradient in 6,12,24 hours induced endothelial cell proliferation inhibition of proliferation inhibition rate, after analysis and statistics significance,to select the most suitable LPS action time (24h) and concentration (10ug/mL), so does to Ras inhibitor FTS, PPAR gamma agonist (rosiglitazone, rosiglitazone) and PPAR (GW9662) gamma antagonist. With the lOug/mL LPS and Ras inhibitors (10 M), PPAR gamma agonist (10 M) and PPAR gamma antagonist (5 M) 24h of the interaction, using immunoblot (Western Blotting) assay for detection of total protein expression of Cx43 in each medicine group.[results] Different concentration gradient of LPS induced inhibition of cell proliferation was significantly, and the inhibition was concentration dependent and time dependent, i.e. over time and concentration increasing, LPS induce the death number of cell increases, there are significant differences compared with the blank control group (P<0.01). The expression of LPS induced Cx43 total protein levels were downregulated with WB protein quantitative analysis, there are significant differences compared with the blank control group (P<0.05). LPS plus FTS group compared with LPS group, the cell proliferation inhibition rate decreased, the expression of Cx43 total protein level increased, the difference was statistically significant (P<0.05). LPS plus rosiglitazone group compared with LPS group the inhibitory rate of cell proliferation decreased, the expression of Cx43 total protein level increased, the difference was statistically significant (P<0.05). LPS and GW9662 cultured group compared with LPS group, cell proliferation inhibition rate decreased, the expression of Cx43 total protein level increased, the difference was statistically significant (P<0.05). LPS, FTS and rosiglitazone cultured group compared with FTS and LPS cultured group, there are no difference in Cx43total protein expression (P>0.05). LPS, FTS and GW9662 cultured group compared with FTS and LPS group, the expression of Cx43 had significant difference in the total protein (P<0.05).[Conclusion] FTS through blocking up the Ras signal pathway can increase the Cx43 total protein expression, so as to exert anti-inflammatory, anti atherosclerosis effect, PPAR agonists can coordinate regulation, effect of Ras inhibitor on the expression of LPS induced Cx43 total protein could be blocked by the PPAR antagonist eliminated, effects on expression of Ras-Rho signal transduction pathway of Cx43 total protein mediated by PPARs.