MicroRNAs in Heart Failure Is the Picture Becoming Less miRky

With 550 000 new cases diagnosed annually and $37 billion spent per year,1 heart failure (HF) with reduced ejection fraction is one of the largest contributors to disease burden and healthcare expenditure in the United States. Despite significant progress in the treatment of HF2,3 with medications, the prognosis of HF remains dismal, with a mortality rate of 42% at 5 years after diagnosis. Therefore, understanding the underlying molecular pathways in the transition from established cardiovascular disease to HF may spur the development of novel biomarkers and therapeutic targets. The heart responds to stressors such as hypoxia (in myocardial infarction [MI]), increased wall stress (in valvular heart disease), and neurohormonal/metabolic stress (in diabetes mellitus and hypertension) by cardiomyocyte hypertrophy and fibrosis. Although initially compensatory for increased wall stress or myocyte loss, the molecular pathways that underlie pathological hypertrophy are ultimately maladaptive, recapitulating further hypertrophy, contractile dysfunction, apoptosis, and fibrosis. The progression to HF is associated with a characteristic cascade of altered intracellular signaling and gene expression, representing a final common pathway to ultimate decompensation. The various signaling pathways that underlie pathological hypertrophy and the progression to HF have been the subject of intense investigation and are summarized in multiple review publications.4–9. More recently, considerable attention has been paid to microRNAs (miRNAs), a novel biological control mechanism with the ability to regulate entire molecular networks by complex feedback and feed-forward mechanisms. Several reviews have summarized recent findings implicating miRNAs in cardiac development and disease.10,11 In the past few years, the discovery of circulating miRNAs has led to their investigation as biomarkers and mediators of cell–cell communication. This review focuses on recent developments detailing the role of miRNAs in the pathogenesis of HF, their potential role as biomarkers, and their use as …