Atherosclerosis is propitiated by a lipid-induced chronic inflammation of the vessel wall. This process is orchestrated by a complex interplay of various cell types, such as endothelial cells (ECs), smooth muscle cells (SMCs), and macrophages. Atherosclerotic lesions preferentially develop at branching points of large arterial tree and the inner curvature of the aortic arch. At these so-called predilection sites, the ECs are constantly exposed to a disturbed blood flow that results in cell dysfunction by upregulating inflammatory genes such as adhesion molecules and chemo- kines (Nam et al. 2009; Weber and Noels 2011). Conversely, a stable or laminar flow exerts anti-inflammatory effects and protects from artery wall thickening by promoting the expression of atheroprotective genes such as Kruppel-like factor 2 (Klf2), Klf4, and eNOS (Dekker et al. 2006). Under the influence of these hemodynamic forces, miRNAs serve as direct mediators of blood flow sensorial mechanisms by interfering with the inflammatory cascade through regulation of signaling pathways or directly modulating the expression of genes implicated in atherosclerosis.
Since 1993 where miRNAs emerged as key regulators of gene expression typically by repressing the target mRNA, the number of publications addressing the interplay of these tiny molecules in regulation has been steadily growing (Lee et al. 1993). Here we outline the most recent concepts on mechanism of action of miRNAs.