title: 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.
authors: Universidad Catolica de Valencia, Guillem de Castro Street 106, 46003 Valencia, Spain.
authors: Irene
authors: I
authors: Sarrion
authors: Department of Pathology, Faculty of Medicine and Odontology, University of Valencia, Blasco Ibáñez Avenue 15, 46010 Valencia, Spain ; Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana (FISABIO), Cataluña Avenue 21, 46020 Valencia, Spain.
authors: Lara
authors: L
authors: Milian
authors: Hospital General Universitario de Valencia, Tres Cruces Avenue, 46014 Valencia, Spain ; Department of Medicine, Faculty of Medicine and Odontology, University of Valencia, Blasco Ibáñez Avenue 15, 46010 Valencia, Spain.
authors: G
authors: G
authors: Juan
authors: Hospital General Universitario de Valencia, Tres Cruces Avenue, 46014 Valencia, Spain ; Department of Medicine, Faculty of Medicine and Odontology, University of Valencia, Blasco Ibáñez Avenue 15, 46010 Valencia, Spain.
authors: Mercedes
authors: M
authors: Ramon
authors: Hospital Universitario Doctor Peset, Gaspar Aguilar Street 90, 46017 Valencia, Spain.
authors: Idelfonso
authors: I
authors: Furest
authors: Department of Pathology, Faculty of Medicine and Odontology, University of Valencia, Blasco Ibáñez Avenue 15, 46010 Valencia, Spain ; Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana (INCLIVA), Blasco Ibañez Avenue 15, 46010 Valencia, Spain.
authors: Carmen
authors: C
authors: Carda
authors: Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Carretera Soller Km 12, Bunyola, Mallorca, 07110 Illes Balears, Spain ; Department of Pharmacology, Faculty of Medicine and Odontology, University of Valencia, Blasco Ibáñez Avenue 15, 46010 Valencia, Spain ; Fundación de Investigación Hospital General Universitario de Valencia, Tres Cruces Avenue 3, 46014 Valencia, Spain.
authors: Julio
authors: J
authors: Cortijo Gimeno
authors: Department of Pathology, Faculty of Medicine and Odontology, University of Valencia, Blasco Ibáñez Avenue 15, 46010 Valencia, Spain ; Fundación para la Investigación del Hospital Clínico de la Comunidad Valenciana (INCLIVA), Blasco Ibañez Avenue 15, 46010 Valencia, Spain ; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Carretera Soller Km 12, Bunyola, Mallorca, 07110 Illes Balears, Spain.
authors: Manuel
authors: M
authors: Mata Roig
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D065627:Familial Primary Pulmonary Hypertension / Q000235:genetics* / Q000473:pathology; D005260:Female; D020869:Gene Expression Profiling; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D035683:MicroRNAs; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D045304:Cytochromes c; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase