Inhibiting Lox-1 Receptor in Macrophages in Atherosclerosis

Abstract

Cardiovascular disease is the leading cause of death in the United States. During the process of plaque development called atherosclerosis, oxidized low-density lipoproteins (oxLDL) penetrate the endothelial lining of the arterial wall. The damage to the endothelial wall induces a signaling pathway to trigger an inflammatory response. Monocytes then phagocytose oxLDL in an attempt to prevent damage to the endothelial wall and ultimately transform into foam cells that constitute plaque tissue. This study explores the prevention of arterial plaque buildup in atherosclerosis using miRNA let-7g. Through bioinformatics, lectin-type oxidized LDL receptor (LOX-1), a macrophage scavenger receptor protein that uptakes oxLDL, leading to foam cell formation, was identified as a potential target. After a thorough literature review, miRNA let-7g was found to be the most promising miRNA that inhibits LOX-1 expression. By preventing the expression of LOX-1, the macrophage will no longer respond to oxLDL signaling and ultimately inhibit plaque development. Our aim was to determine if LOX-1 expression in macrophages would increase in a dose dependent manner in response to increased oxLDL concentrations. LOX-1 expression in human macrophage primary cell cultures was measured using a flow cytometry assay. We found that oxLDL concentration was not correlated with macrophages’ expression of LOX-1 receptor in a dose-dependent manner. This suggests that inflammatory signaling molecules are needed for LOX-1 upregulation and increased oxLDL uptake. It is expected that using let-7g in conjunction with an anti-inflammatory compound, such as rapamycin, will further inhibit oxLDL uptake by macrophages and result in a novel treatment for atherosclerosis.