Role of circulating miRNAs as biomarkers in idiopathic pulmonary arterial hypertension: possible relevance of miR-23a

Oxid Med Cell Longev. 2015;2015:792846. doi: 10.1155/2015/792846. Epub 2015 Feb 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / metabolism
  • Cells, Cultured
  • Cytochromes c / genetics
  • Cytochromes c / metabolism
  • Familial Primary Pulmonary Hypertension / genetics*
  • Familial Primary Pulmonary Hypertension / pathology
  • Female
  • Gene Expression Profiling
  • Heme Oxygenase-1 / genetics
  • Heme Oxygenase-1 / metabolism
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • NF-E2-Related Factor 2 / genetics
  • NF-E2-Related Factor 2 / metabolism
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • Biomarkers
  • MicroRNAs
  • NF-E2-Related Factor 2
  • NFE2L2 protein, human
  • PPARGC1A protein, human
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Transcription Factors
  • Cytochromes c
  • Heme Oxygenase-1
  • Superoxide Dismutase