Abstract 16926: First Global Assessment of Circulating Plasma MicroRNAs as Potential Biomarkers for Pulmonary Arterial Hypertension
Background: Circulating extracellular microRNAs (miRNAs) have been identified as possible biomarkers in cancer and some cardiovascular diseases, but as yet their levels have not been examined in the plasma of patients with pulmonary arterial hypertension (PAH). Hypothesis: Altered levels of circulating miRNAs will provide insight into underlying mechanisms of PAH and serve as disease-specific biomarkers.
Methods: A global screen of 1066 different miRNAs was performed with a discovery cohort of 4 treatment-naive patients with idiopathic (I) PAH and 3 healthy controls (age and sex matched). Total RNA was extracted from plasma and profiled with a miRNA (RT)-qPCR array platform (Qiagen). A separate cohort of 13 healthy controls and 14 PAH patients (8 associated (A) and 6 IPAH) was used for validation purposes. MicroRNA expression levels were normalized with a mean-centering restricted method in the discovery cohort, and 2 novel internal reference genes were used in the validation cohort.
Results: 436±45 miRNAs were detectable (PCR Cq cutoff < 35) in patient plasma samples in the discovery cohort. 25 different miRNAs were differentially expressed (p<0.05) in PAH vs. control groups (12 miRNAs down, 13 miRNAs up; from -3.2 to 3.5 fold change). The differential expression was confirmed in 4 of 10 miRNAs that were examined in the validation cohort, including let-7g, which was 1.4-fold lower in PAH patients compared to healthy controls (p=0.004). The area under the receiver-operator characteristic curve of let-7g was 0.82 (p=0.004), suggesting that this miRNA can distinguish between PAH and healthy individuals with significant sensitivity and specificity. No unique plasma miRNA was found to distinguish between IPAH and APAH.
Conclusion: This first global assessment of circulating miRNAs in IPAH supports their utility as non-invasive biomarkers for disease activity.
- © 2012 by American Heart Association, Inc.