MicroRNAs as therapeutic targets in atherosclerosis

Xavier Loyer, Ziad Mallat, Chantal M Boulanger, Alain Tedgui
Expert Opinion on Therapeutic Targets 2015, 19 (4): 489-96

INTRODUCTION: Atherosclerosis is a chronic inflammatory disease of the arterial wall. A number of phenotypic cell changes occur during the development and progression of atherosclerosis. MicroRNAs (miRNAs) are key regulators of gene expression that act at the post-transcriptional level. They have been implicated in cardiovascular diseases, including atherosclerosis.

AREAS COVERED: This review provides an overview of our knowledge about the expression and the roles of miRNAs in different cell types involved in atherosclerosis, with a focus on experimental strategies to modulate miRNA expression and their therapeutic effects in animal models of atherosclerosis. miRNA expression is regulated by inflammatory conditions and by shear stress in endothelial cells. Therapeutic approaches using antagomiR and miRNA mimic delivery and have been shown potentially effective in atherosclerosis. Moreover, a large body of evidence exists supporting a role for not only intracellular miRNA, but also miRNA carried by extracellular vesicles that are involved in inter-cellular communication through the transfer of miRNA.

EXPERT OPINION: Modulation of miRNA expression could represent novel innovative therapeutic approaches to treat atherosclerosis by targeting a single cell type or specific pathways. Future challenges will consist in deciphering the mechanisms involved in miRNA regulation and in improving cell-specific delivery of 'miR-drugs' by alternative strategies, including miRNA-enriched micro vesicles.

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