MicroRNAs: Important Modulators of oxLDL-Mediated Signaling in Atherosclerosis

Oxidized low-density lipoprotein (oxLDL) is known to be a major risk factor for the initiation and development of atherosclerosis. It can elicit an array of atherogenic responses in multiple types of cells residing in the arterial wall, such as endothelial cells (ECs), macrophages, dendritic cells (DCs), and vascular smooth muscle cells (VSMCs). Although they have been studied for many years, the detailed mechanisms modulating oxLDL-induced inflammation have not been fully elucidated. Epigenetic mechanisms consist of DNA methylation, histone post-translational modifications (PTMs), and microRNA (miRNA) alterations. Recently, epigenetic factors, especially miRNAs, have emerged as novel components of the gene expression regulating oxLDL-triggered signal transduction. In addition to their regulatory roles in signaling molecules, increasing evidence suggests that the different genetic stability and cross-talk regulation among these epigenetic factors may be particularly important to the sustained inflammation initiated by temporal oxLDL stimulation. Therefore, in this review, we primarily focused on the functional role of miRNAs, as well as other epigenetic factors, on modulating oxLDL-induced signal transduction in different vascular cells, with a special emphasis on the crosstalk interactions between miRNAs and other epigenetic players that help translate transient environment insults into chronic inflammation. Moreover, we extensively discussed the potential applicability of miRNAs as disease biomarkers and therapeutic targets in diagnosing and treating atherosclerosis. J Atheroscler Thromb, 2013; 20:215-227.