Role of Circulating miRNAs as Biomarkers in Idiopathic Pulmonary Arterial Hypertension: Possible Relevance of miR-23a

Abstract

Idiopathic pulmonary hypertension (IPAH) is a rare disease characterized by a progressive increase in pulmonary vascular resistance leading to heart failure. MicroRNAs (miRNAs) are small noncoding RNAs that control the expression of genes, including some involved in the progression of IPAH, as studied in animals and lung tissue. These molecules circulate freely in the blood and their expression is associated with the progression of different vascular pathologies. Here, we studied the expression profile of circulating miRNAs in 12 well-characterized IPAH patients using microarrays. We found significant changes in 61 miRNAs, of which the expression of miR23a was correlated with the patients' pulmonary function. We also studied the expression profile of circulating messenger RNA (mRNAs) and found that miR23a controlled 17% of the significantly changed mRNA, including PGC1α, which was recently associated with the progression of IPAH. Finally we found that silencing of miR23a resulted in an increase of the expression of PGC1α, as well as in its well-known regulated genes CYC, SOD, NRF2, and HO1. The results point to the utility of circulating miRNA expression as a biomarker of disease progression.

miR‐1 is increased in pulmonary hypertension and downregulates Kv1.5 channels in rat pulmonary arteries

“…Among the miRNAs found in the literature that were increased in PAH but had not been previously functionally characterized with respect to PA function, miR‐1 was the one with the highest upregulation (8‐fold increase in microarray experiments and 12‐fold increase in the validating PCR analysis) in plasma from 12 idiopathic PAH patients (Sarrion et al . ). miR‐1 is also upregulated in peripheral blood mononuclear cells in essential hypertensive patients (Kontaraki et al .…”

Downregulation of microRNA‑374a predicts poor prognosis in human glioma

“…The values of the quantification cycle (Cq) that were obtained for quantification were used for the calculation of fold changes in miRNA abundance according to the 2 -ΔΔCq method (15). The raw data were processed by the following workflow: Background detection, RMA global background correlation, quantile normalization, median polish adjustment was performed and log2-transformation with miRNA QC tool software (Affymetrix; Thermo Fisher Scientific, Inc.) (16).…”

Translational Advances in the Field of Pulmonary Hypertension.Translating MicroRNA Biology in Pulmonary Hypertension. It Will Take More Than “miR” Words

“…For example, circulating levels of miR-150 (72), miR-26a (73), miR-23a (74), and miR-125a (75) have been reported as reduced in patients with PAH. Dysregulation of entire sets of circulating miRNAs in PAH has also been described (74,76). Other miRNAs with known causative actions in PAH, such as the miR-130/301 family (20) and miR-210 (14), have been found to be elevated in the pulmonary circulation of patients with PH.…”