Roles of microRNAs in atherosclerosis and restenosis

Abstract

Atherosclerosis is commonly appreciated to represent a chronic inflammatory response of the vascular wall, and its complications cause high mortality in patients. Angioplasty with stent replacement is commonly performed in patients with atherosclerotic disease. However, the restenosis usually has a high incidence rate in angioplasty patients. Although the pathophysiological mechanisms underlying atherosclerosis and restenosis have been well established, new signaling molecules that control the progress of these pathologies have continuously been discovered. MicroRNAs (miRs) have recently emerged as a novel class of gene regulators that work via transcriptional degradation and translational inhibition or activation. Over 30% of genes in the cell can be directly regulated by miRs. Thus, miRs are recognized as crucial regulators in normal development, physiology and pathogenesis. Alterations of miR expression profiles have been revealed in diverse vascular diseases. A variety of functions of vascular cells, such as cell differentiation, contraction, migration, proliferation and inflammation that are involved in angiogenesis, neointimal formation and lipid metabolism underlying various vascular diseases, have been found to be regulated by miRs. This review summarizes current research progress and knowledge on the roles of miRs in regulating vascular cell function in atherosclerosis and restenosis. These discoveries are expected to present opportunities for clinical diagnostic and therapeutic approaches in vascular diseases resulting from atherosclerosis and restenosis.

Figure 1

The canonical pathway of miR processing. The primary miR (pri-miR) are transcripted by either RNA polymerase II or III from independent gene in the nucleus. In the following processing, the microprocessor complex (Drosha-DGCR8) processes pri-miR into a ~60-100-nucleotide precursor hairpin (pre-miR). The resulting pre-miR is exported to the cytoplasm by Exportin-5-Ran-GTP. In the cytoplasm, the RNase III Dicer and TRBP cleave the pre-miR into ~22-nucleotide miR/miR* duplex. One strand termed as guide strand, further representing a mature miR, the miR* termed as passenger strand, which undergoes degradation rapidly. Mature miR is incorporated into a miRISC and base-paired to its target mRNAs for mRNA degradation or translational repression.