Associations Between Chemokines CCL19and CCL21and Their Receptor CCR7and Coronary Artery Disease

ObjectiveInflammation plays an important role in the pathogenesis of atherosclerosis,the recruitment and adhesion of inflammatory cells into the vessel wall is thebegining of vascular inflammation, this is also the significant pathologicalcharacteristic of inflammatory vascular diseases such as atherosclerosis.Chemokine is a kind of cytokines which could direct migration of lymphocytes,recently studies found that the homeostatic chemokines CCL19and CCL21andtheir corresponding receptor CCR7play an important role in atherosclerosis.This study aimed to establish the relationships between CCL19, CCL21, andCCR7gene variants and coronary artery disease in a Chinese Han population,and to identify the role of the homeostatic chemokines CCL19and CCL21andtheir common receptor CCR7in atherogenesis.MethodsTen tagSNPs were retrieved from the Hapmap database for Hanpopulation samples in the CCL19, CCL21and CCR7genes and2.0KB regionson each side. In1746cases of the north group and700cases of the southgroup, the SNP genotypes were detected by polymerase chain reaction-directsequencing method and the associations between every SNP genotypes andalleles and coronary heart disease, and associations between plasma CCL19and CCL21level and SNP genotypes were analysised. Collect atherosclerosis and normal human coronary arteries, and use the immunohistochemicalstaining to detect the experssion of CCL19,CCL21and CCR7. Detect the role ofCCL19,CCL21and CCR7in THP-1cells adhereing and migrating to the Humanumbilical vein endothelial cells (HUVECs).Results(1) CCL19gene rs2227302T allele, CCL21rs2812377G allele and CCR7gene rs588019A allele frequencies in the coronary heart disease group aresignificantly higher than the control group, increasing the risk of coronary heartdisease (P<0.001, P=0.004, P=0.002).(2) CCL19, CCL21and CCR7expressions were increased markedly in coronary atherosclerotic plaque than innormal coronary artery, and they were all increase gradually along with theprogress of atherosclerosis.(3) CCL19/CCL21-CCR7can promotes THP-1cellsmigrate to HUVECs and CCL19also can promotes the adhesion betweenTHP-1and HUVECs.ConclusionsCCL19/CCL21-CCR7is a novel homeostatic chemokine system thatassociated with incident CAD risk in Chinese Han individuals and modulateshuman monocyte adhesion and migration to HUVECs, promoting atherogenesis.These data suggest that the CCL19/CCL21-CCR7axis plays an important rolein atherosclerosis progression.