Effect Of Profilin-1on Vascular Remodeling Induced By AGEs And Possible Mechanism

OBJECTIVE:A large number of studies have shown that Advanced Glycation End Products (AGEs) was related with diabetes vascular lesions complications and atherosclerosis. The reorganization and redistribution of actin is the main pathological basis of endothelial cell shrinkage and increased vascular permeability, which is mediated by actin regulatory proteins profiling-1. Studies have reported that the expression of profiling-1in artery atheromatous plaque of the patients with coronary heart disease (CHD) is increased. But, whether it has played a key role in diabetes vascular lesions have not see related reports. This topic is to discuss the profiling-1levels and receptor for advanced glycation end-products levels in plasma of diabetic patients with coronary heart disease and the correlation study between them and coronary artery stenosis degree of. And do further study in vascular lesions model of rats which was induced by exogenous AGEs and in vitro cultured aorta smooth muscle cells, and explore the role profilin-1in vascular remodeling induced by AGEs and related pathways. Just for new targets of anti vascular lesions occuring to provide theoretical basis.METHODS:1. Selection of31patients with coronary heart disease (CHD) and31cases of diabetic patients with coronary heart disease (CHD) and27cases of healthy subjects, in the case of the informed consent, collect the blood specimen, and detect the profilin-1and RAGE levels in plasma by Elisa kits.2. Inducing vascular injury model by SD rat caudal vein injection with AGEs-BSA (25mg/kg, i.v. qd,2month). Using HE staining, Mallory staining and immunohistochemical (IHC) test organization morphological changes and changes of related indicators. Using western blot and real time PCR to detect the expression of profilin-1in aorta tissue.3. With the vitro cultured rat aortic smooth muscle cells, using different concentrations of exogenous AGEs deal with different time, and then to detect smooth muscle proliferation by MTT method. Western blot, real time PCR was used to detect the expression of profiling-1, JNK and STAT3.RESULTS:1. Compared with normal control group, Profilin-1and RAGE levels in plasma of CHD group and CHD with DM group increased significantly. The linear regression showed that the degree of coronary stenosis and the profilin-1level, RAGE level in plasma were positively correlated. And the profilin-1level in plasma and RAGE level in plasma were positively correlated.2. Compared with normal control group,HE staining showed the aorta of rats, which were dealed with AGEs had obvious morphological changes, and the vascular remodeling index of MT/LD, MA/LA, smooth muscle layer were increased significantly, IHC protein quantitative displays the average optical density value (the Average optical density, AOD) and the area ratio of expression and integral optical density(Integral optical density, IOD) of profilin-1in each group increased significantly, Western blot and real time PCR showed an increased profiin-1expression on aorta.3. The in vitro cultured aortic smooth muscle cells, the results show that with the increase of concentration of AGEs after its first proliferation is restrained, under the same drug concentration processing, with the extension of time after its first proliferation it is restrained. Western blot and real time PCR results showed that the gene expression and protein expression in consistent, related pathways results show profilin-1was STAT3dependence regulation, while the JNK expression is reduced, and its related pathway inhibition test due to the time limit has not been completed.CONCLUSION:1. The profiling-1levels and RAGE levels in plasma were positively correlated, and both are positively associated with the degree of coronary artery stenosis;2. The expression of profilin-1in the vascular remodeling model of rats induced by AGEs is increased;3. AGEs induced proliferation of RASMCs and JNK-STAT3pathway may be involved in the process.