Toward systems biology of pulmonary hypertension.

In this issue of Circulation, Parikh and colleagues1 present an elegant study that lies at the intersection of 2 recent major developments in cardiovascular research—the recognition of the role of microRNAs in normal and abnormal cardiovascular biology, and the introduction of computational systems biology approaches to elucidate the mechanisms of cardiovascular disease. This work provides convincing evidence for the central role of microRNA-21 (miR-21) in the pathogenesis of pulmonary hypertension (PH) generally and pulmonary arterial hypertension (PAH) more specifically, and suggests a potential 2-hit rationale for incomplete penetrance of mutations in BMPR2 in heritable PAH.