Role of microRNAs in cardiac development and disease.

Abstract

Heart disease-related deaths are the highest in most societies and congenital heart diseases account for approximately 40% of prenatal deaths and over 20% of mortality in the first few months after birth. Congenital heart disease affects approximately 1% of all newborns and is the causative factor for more deaths within the first year of life as compared to all other genetic defects. Advances in treatment approaches increased life expectancy and led to an expansion of adult population with clinical manifestation of congenital heart defects in up to 90% of the children born with congenital heart diseases. Regulation of cardiac gene expression involves multiple independent enhancers that play a critical role in maintaining a restricted and specific pattern of gene expression in the heart. Cardiac transcriptional pathways are intimately regulated by microRNAs (miRNAs), which are small, regulatory RNAs, approximately 22 nucleotides in length, also coded by specific genes. These miRNAs act as suppressors of gene expression by inhibiting translation and/or promoting degradation of target protein-coding mRNAs. There are several miRNAs involved in the development of heart and dysregulation of specific miRNAs is associated with congenital and other cardiac defects. Stress responsive cardiac hypertrophy is orchestrated among other factors, by specific miRNAs. miRNAs such as miR-499 are considered useful as biomarkers of a given heart disease. Therapeutic application of miRNAs is also envisaged considering the small size and specific effects of these molecules. In this review, we addressed different roles of miRNAs in the development and diseases of the heart.