There is increasing interest in small noncoding RNA molecules known as microRNAs (miRNAs) as potential markers and mediators in vascular disease (1). miRNAs are well known for their pervasive control of gene expression within cells, but far less is known about the extracellular function of miRNAs that circulate in the blood (2). Nevertheless, a growing number of studies have demonstrated the potential utility of circulating miRNAs as biomarkers for various pathophysiological conditions, including, most recently, pulmonary arterial hypertension (PAH), in which reduced plasma levels of miR-150 were shown to be predictive of poor survival (3). Circulating miRNAs represent attractive biomarker candidates because of their high stability (4), noninvasive source, and amenability to polymerase chain reaction (PCR)-based amplification, which can allow for the detection of changes even at very low levels. Moreover, perturbations in specific miRNA plasma levels may reflect changes in vascular homeostasis or tissue injury. Therefore, circulating miRNAs extracted from human plasma could also provide unique insight into the underlying mechanisms of PAH that are directly relevant to the human disease.

Here, we conducted unbiased global miRNA screens of plasma from patients with PAH and rats with monocrotaline (MCT)-induced pulmonary hypertension (PH). We reasoned that concordant alterations in plasma levels between experimental and clinical PH would identify miRNAs more likely to be robust markers of disease activity, and possibly also contribute to the pathobiology of PAH. Some of the results of these studies have been previously reported in the form of abstracts (5, 6).