PURPOSE: Idiopathic Pulmonary Hypertension (IPAH) is a devastating disease that despite new therapies carries a poor prognosis. There is a need for development of surrogate and therapeutic biomarkers. MicroRNAs (miRNAs) are 21-25 nucleotide sequences known to interact with targets through degradation of mRNA or inhibition of protein translation. MicroRNAs have been implicated in the pathogenesis of malignancies, cardiac, neurological and renal disease. We hypothesized that circulating miRNAs are detectable in the serum of patients with IPAH and they are dysregulated in patients with IPAH compared to normal controls.
METHODS: We analyzed serum from the pulmonary artery (PA) and peripheral venous circulation in 11 patients with IPAH (mean age= 41.5 years, mpa=48.27mmhg) and 4 normal subjects (mean age= 54 years, mpa=18.75 mmhg).. RNA was isolated from 200 microliters of serum and followed by qPCR analysis for expression of six specific miRNAs ; miR-155, miR-146a (inflammatory), miR-126 (vascular specific), miR-206, miR-21, miR-210 (hypoxia responsive). Exogenous C. elegans spike in was used as endogenous control for RNA isolation and miRNA expression.
RESULTS: MicroRNAs were detected in PA serum and in peripheral blood. Patients with IPAH demonstrated dysregulated circulating miRNA expression (elevated miR- 155, 146A and reduced miR-126) compared to normal controls. The observed differences were most significant in the peripheral blood serum.
CONCLUSION: We have demonstrated that 1: circulating miRNA are detectable in patients with IPAH 2. IPAH patients exhibit altered expression of inflammatory miRNA (155, 146A) compared to normal control patients and 3) Patterns of miRNA expression differ depending on the locale of blood sampling. This is an initial evaluation of potential candidate miRNA biomarkers in IPAH, a more extensive evaluation of all known human miRNA is ongoing as is evaluation of miRNA expression in peripheral blood cell.
CLINICAL IMPLICATIONS: To our knowledge this represents the first examination of circulating miRNA in both the arterial and venous circulation of patients with IPAH. The primary goal is to determine whether non-invasive miRNAs may serve as biomarkers for either diagnosis or therapeutic response in IPAH.
DISCLOSURE: Namita Sood, No Financial Disclosure Information; No Product/Research Disclosure Information