Role of CXCR۳ chemokine receptor in the development of endothelial dysfunction

Background and Aim: Atherosclerosis is a chronic progressive vascular disease and remains the leading cause of death and morbidity worldwide. Endothelial dysfunction is an important factor in the progression of atherosclerotic cardiovascular disease. The endothelium is a community of endothelial cells (ECs), which line the blood and vessels. The increased expression of adhesion and pro-inflammatory markers leads to abnormal endothelium-dependent function. Adhesion (I-CAM-۱ and V-CAM-۱) and inflammatory (IL-۶ and NFK-B) markers are some of the most important endothelial markers in the progression of atherosclerosis. Chemokines receptors play important roles in atherosclerotic vascular disease. CXCR۳ is a G-protein-coupled cell surface chemokine receptor expressed by endothelial cells (ECs). The clinical relevance of CXCR۳ binding chemokines in heart disease is not fully understood. In this study, we evaluated the effect of CXCR۳ downregulation on the expression level of adhesion and inflammation markers related to endothelial dysfunction.Methods: An mRNA-cleaving oligodeoxynucleotide (DNAzyme) designed for the CXCR۳ transcript. HUVEC cell line as an endothelial model was maintained in DMEM containing ۱۰% FBS. CXCR۳ DNAzyme transfected to the HUVEC cell line with TurboFectTM. Following CXCR۳ downregulation confirmation, the mRNA expression level of I-CAM-۱, V-CAM-۱, IL-۶ and NFK-B genes were examined with q-RT PCR method Results: The expression level of I-CAM-۱, V-CAM-۱, IL-۶, NFK-B genes were showed significant up-regulation in transfected HUVEC cell line compare with control HUVEC cell line.Conclusion: Our results showed that reducing the expression of the CXCR۳ gene could induce endothelial dysfunction through the change of adhesion and inflammation markers genes expression. Therefore, this receptor may be considered as a potential molecular target for the treatment of atherosclerosis

Keywords:

Atherosclerosis , Endothelial dysfunction , CXCR۳ , Inflammation markers , Adhesion markers