MicroRNAs in vascular disease

Abstract

MicroRNAs (miRNAs) are a novel class of endogenous, small, noncoding RNAs that regulate gene expression via degradation, translational inhibition, or translational activation of their target messenger RNAs. Functionally, an individual miRNA is important as a transcription factor because it is able to regulate the expression of its multiple target genes. As a group, miRNAs are able to directly regulate at least 30% of genes in a cell. In addition, other genes may also be regulated indirectly by miRNAs. It is therefore not surprising that miRNAs could be the pivotal regulators in normal development, physiology, and pathology. Recent studies have identified that miRNAs are highly expressed in vasculature and their expression is dysregulated in diseased vessels. miRNAs are found to be critical modulators for vascular cell functions such as cell differentiation, contraction, migration, proliferation, and apoptosis. Accordingly, miRNAs are involved in the vascular dysfunction, ischemic angiogenesis, reendothelialization, and vascular neointimal lesion formation under diverse vascular diseases. miRNAs may serve as novel therapeutic targets for vascular diseases such as impaired angiogenesis or reendothelialization, restenosis, atherosclerosis, hypertension, and diabetic vascular complication. This review article summarizes the research progress regarding the roles of miRNAs in vascular diseases.

Figure 1. The biological functions of miR-143/145 and their identified target gens

Kruppel-like factor 4 (KLF4), kruppel-like factor 5 (KLF5), myocardin (Myo), Calmodulin kinase II delta (CamkIIδ), Ets-like protein 1(Elk-1), angiotensin I-converting enzyme (ACE), Junctional Adhesion Molecule A (JAM-A), fascin (Fasc), Friend leukemia virus integration 1 gene (FLI1), Fascin homolog 1 (FSCN1), Yamaguchi sarcoma (YES), activator of transcription 1 (STAT1), mucin 1 (MUC1), versican, adducin3 (add3), DNA methyltranferase 3A (DNMT3A), V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS), extracellular signal-regulated kinase-5 (ERK5).