Abstract 495: MicroRNA-155 Modulates Endothelial Intracellular Adhesion Molecule-1 Expression

Abstract

The endothelium is essential in maintaining vascular tone, thrombosis, vascular remodeling, signal transduction, and inflammation by directly producing cytokines and chemokines which act in cell signaling and the recruitment of lymphocytes. In addition, the up-regulation of adhesion molecules such as vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), E-selectin, and P-selectin aid in leukocyte adherence and diapedesis. This collective alteration in the physiological characteristics of endothelial cells is commonly referred to as endothelial activation. Currently, microRNA regulation of endothelial cell activation remains poorly characterized. Specifically, microRNA-155 (miR-155) has been found to play an important role in the development and function of several immune cell types such as dendritic cells, macrophages, B-cells, and T-cells. However, the capacity of miR-155 to participate in a phenotypic change in non-traditional immune cells to a pro-inflammatory state has yet to be examined. In order to address this short-coming, our research focuses on whether the expression miR-155, affects endothelial activation. Thus far, we have determined that the expression of miR-155 can be modulated by pro-inflammatory mediators traditionally associated with endothelial activation such as disturbed flow, TNF-α, IL-1β and lipopolysaccharide. In addition to its inducible expression within endothelial cells, we have found that miR-155 can specifically alter ICAM-1 expression. Western blots with protein from excised aortas of miR-155 -/- mice reveal significantly reduced ICAM-1 expression when compared to WT mice. This data was further confirmed in vitro with protein gathered from cultured mouse aortic endothelial cells. Additionally, in accordance with the modulated ICAM-1 expression, we found monocyte adhesion to endothelial cells over-expressing miR-155 to be increased. In conclusion, these preliminary findings suggest that miR-155 plays a major role in endothelial activation, and therefore regulation of miR-155 expression holds significant therapeutic potential in the treatment of cardiovascular diseases.