The effect of chemokine CXCR3 receptor downregulation on vascular endothelial cell dysfunction

Sajjadi, Seyedeh Fatemeh; Boroumand, Mohammad Ali; Behmanesh, Mehrdad

The effect of chemokine CXCR3 receptor downregulation on vascular endothelial cell dysfunction

Document Type : Original Research

Authors

Seyedeh Fatemeh Sajjadi ¹

mohammad ali boroumand ²

Mehrdad Behmanesh ³

¹ Department of Genetics, Faculty of Biological Science, Tarbiat Modares University, Tehran, Iran

² Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran

³ Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran.

Abstract

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.

Keywords

Atherosclerosis

Endothelial dysfunction

CXCR3

Tight junction

Adhesion markers

20.1001.1.23222115.1399.11.3.6.9

Subjects

Molecular biotechnology

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