miRNA208/Mef2 and TNF-α in Right Ventricular Dysfunction: The Transition From Hypertrophy to Failure

Pulmonary arterial hypertension (PAH) is a rare but progressive and deadly disease caused by functional and structural changes in the pulmonary vasculature, which lead to an increase in pulmonary vascular resistance. Regardless of the initial pathogenic trigger, the major causes of increased pulmonary vascular resistance in patients with PAH are sustained pulmonary vasoconstriction, pulmonary vascular remodeling, in situ thrombosis, and increased pulmonary vascular wall stiffness. Despite expanding research into the diagnosis and treatment of pulmonary hypertension, death rates from pulmonary hypertension have continued to increase 2.5% per year for women and 0.9% per year for men during the past decade.1 Patients with PAH, if untreated, die mainly because of progressive right heart failure, and the response of the right ventricle (RV) to the increased afterload is an important determinant of outcome in patients.2 During the development of pulmonary hypertension, an initial adaptive response of the RV to the increased afterload is to increase its wall thickness and contractility with varying degrees of RV hypertrophy.3 However, with disease progression, sustained long-term pressure overload of the RV can lead to progressive contractile dysfunction and eventually cause RV failure with further RV dilation. Little is known about the molecular and cellular mechanisms, which underlie the development of RV failure. The mechanism that determines the transition of RV function from compensated hypertrophy to decompensated failure is also uncertain. Article, see p 56 MicroRNAs (miRNAs), as crucial regulators of cardiovascular development and cardiac remodeling, have attracted increasing interest in recent years. Drake et al4 compared the gene expression patterns between RV hypertrophy in hypoxia-induced …