Homocysteine Mediated MCP-1 Expression Through P38/MAPK And Its Relationship With Carotid Atherosclerosis

Objective To investigate the correlation between serum homocysteine(Hcy)level and carotid atherosclerosis and the effect on the expression of monocyte chemotactic protein-1(MCP-1)in human umbilical vein endothelial cells.Method We selected clinical data of 226 patients with ischemic stroke hospitalized in Anhui provincial committee hospital from January 2016 to November 2017.According to the results of carotid ultrasound,226 patients were divided into normal carotid artery group(91 cases),intimal thickening group(24 cases),carotid artery plaque group(100 cases)and carotid artery stenosis group(11 cases).Total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C),low-density lipoprotein cholesterol(LDL-C),uric acid(UA)and homocysteine(Hcy)were measured by biochemical analyzer.Human umbilical vein endothelial cells were cultured in vitro,HUVEC was treated with different concentrations of Hcy in the medium.The expression level of MCP-1 was detected by real-time quantitative PCR.The level of MCP-1 and the changes of p38 and its phosphorylated protein in human umbilical vein endothelial cells were analyzed by Western blot.Result We collected clinical data from 226 patients,including 141 males and 85 females.According to the results of carotid ultrasonography,they were divided into four groups.Among them,91 patients in the normal carotid intima group were 72.49±8.55 years old with plasma Hcy concentration of 12.74±4.17umol/L.24 patients in the carotid intima thickening group were 72.92±7.35 years old with plasma Hcy concentration of 17.78±6.50umol/L.100 patients in the carotid intima plaque group were 75.23±8.12 years old with plasma Hcy concentration of 17.53±6.83umol/L,and 11 patients in the carotid intima stenosis group were 76.64±9.71 years old.The plasma Hcy concentration was 19.24±8.74umol/L.There were no statistically significant differences in age,gender,proportion of patients with hypertension,proportion of patients with diabetes,Body mass index(BMI),TC,TG,LDL-C and UA levels among the four groups(all P >0.05).Compared with the normal group,the HDL-C level in the stenosis group was statistically significant.Compared with the normal group,the levels of Hcy in the intima-thickening group,the plaque group and the stenosis group were significantly increased,with statistically significant differences(P < 0.05).Human umbilical vein endothelial cells were cultured in vitro and treated with different concentrations of Hcy.The gene expression of MCP-1 was significantly increased by real-time quantitative PCR detection.The phosphorylation level of p38 was increased by western-blot analysis,and the expression of MCP-1 was decreased after the use of p38 inhibitor(SB203580).Conclusion 1.Hcy level may be a risk factor of carotid atherosclerosis.2.Hcy increased the level of inflammatory cell factor MCP-1 through p38 MAPK pathway leading to atherosclerosis in vitro.