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Abstract: Hyperglycemia is a major cause of diabetes. Hyperglycemia-induced endothelial dysfunction is generally believed to be the basis of diabetic vascular complications such as retinopathy, nephropathy and cardiovascular diseases. The most important molecules in endothelial cells that can sense elevated level of glucose and transmit signals into the cell are G protein-coupled receptors (GPCRs).
In the present study, according to bioinformatics analysis of genomic sequences between healthy and patient individuals, two G proteins GPR182 and CALCRL were selected and their expression level were examined in hyperglycemic and normal conditions in HUVEC as a model of vascular endothelial cells at different glucose concentrations and various time intervals. In addition, the effects of hyperglycemia on cell viability and cell cytotoxicity were assessed by MTT and LDH assay respectively and also morphological changes by immunohistochemistry.
Overall our data reveal a probable role for GPR182 and CALCRL in hyperglycemia-induced endothelial dysfunction. Thus, they could be developed as a potential molecular targets for the endothelial dysfunction therapy.

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Atherosclerosis is a chronic vascular disease and remains the leading cause of death and morbidity worldwide. Endothelial dysfunction is an important factor in the progression of atherosclerotic disease. Increased expression of cell adhesion index genes and decreased cell-binding proteins lead to abnormal endothelial function. These molecular changes are one of the most important indicators of endothelial cell dysfunction and the progression of atherosclerosis. CXCR3 is a G-protein-coupled chemokine receptor expressed by endothelial cells. The role of the receptor CXCR3 and its ligands in endothelial cells and heart disease is not yet fully understood. In this study, we evaluated the effect of CXCR3 downregulation on the expression level of adhesion (I-CAM-1, V-CAM-1), tight junction (TJP1), related to endothelial dysfunction.
In order to reduce the expression of the CXCR3 gene, the RNA-cleaving DNAzyme was used against the mRNA of the CXCR3 gene. DNAzyme was transfused into HUVEC cells by TurboFect^TM. After confirmation of decreased CXCR3 gene expression, RNA extraction and cDNA synthesis were performed and then the expression of markers was evaluated by RT-qPCR technique.
Our result was showed the expression level of I-CAM-1 and V-CAM-1 were showed significant up-regulation in transfected cells compared with control cells, while the TJP1 gene was not showed significant change. It seems that reducing the CXCR3 gene expression could induce endothelial dysfunction through the change of adhesion markers genes expression. Therefore, this receptor can be considered as a potential molecular target for a better understanding of the mechanism of atherosclerosis.