MicroRNA expression in heart failure

Abstract

MicroRNAs (miRs) are key regulators of gene expression during both normal and pathophysiological states. In the cardiac context, miRs are known to be involved in developmental processes as well as to be differentially regulated in various forms of heart disease. What is less clear is whether changes in the expression of specific miRs are secondary to heart failure or, rather, an underlying cause of the phenotype. Although changes in miR expression in and of themselves may be useful biomarkers of disease progression, they also have the potential to be predictors of therapeutic response. Predictive potential is enhanced further by simultaneous co‐analysis of mRNA expression and an examination of the interrelationship between miRs and their putative mRNA targets. Changes in miR expression that are potentially causal or maladaptive in the context of heart failure have been examined in animal models of miR mimic/inhibitor overexpression or miR knockout. Although these studies highly useful, they may not recapitulate all conditions found in human heart failure. A novel means of approaching miR regulation in humans is to examine changes in myocardial miR expression that are directionally reversible in patients that are responders versus non responders to heart failure therapeutic agents. Results of preliminary studies will be discussed.