A New Level of Complexity The Role of MicroRNAs in Cardiovascular Development

The discovery of the regulatory role of noncoding RNAs, and micro (mi) RNAs in particular, has added a new layer of complexity to our understanding of cardiovascular development. miRNAs regulate and modulate various steps of cardiovascular morphogenesis, cell proliferation, differentiation, and phenotype modulation. miRNAs simultaneously regulate multiple targets, and many miRNAs can bind to the same target, allowing for a complex pattern of regulation of gene expression. miRNA families are continuously added during evolution paralleling the increased complexity of the cardiovascular system in vertebrates compared with invertebrates. Several lines of evidence suggest that the appearance of miRNAs is at least in part responsible for the formation of complex organ systems and stable regulatory mechanisms in vertebrates. We review the current understanding of miRNAs during cardiovascular development. Further progress in this area will help to decipher quantitative changes in gene expression that provide robustness to cellular phenotypes and regulatory options to diseases processes. miRNAs might also provide clues to better understand congenital heart defects, which are the most common birth defects in human newborns. (Circ Res. 2012;110:1000-1013.)