MicroRNA Dysregulation in Pulmonary Arteries from Chronic Obstructive Pulmonary Disease. Relationships with Vascular Remodeling

• DOI: 10.1165/rcmb.2017-0040oc
• Publication Date: 2018-05-14T16:17:50Z
• Authors: Melina M. Musri; Núria Coll-Bonfill; Bradley A. Maron; Víctor I. Peinado; Rui-Sheng Wang; Jordi Altirriba; Isabel Blanco; William M. Oldham; Olga Tura-Ceide; Jessica García-Lucio; Benjamin de la Cr...; Gunter Meister; Joseph Loscalzo; Joan A. Barberà
• Keywords: Male; MICRORNAS; Myocytes, Smooth Muscle; SMOOTH MUSCLE CELL PHENOTYPIC SWITCH; Pulmonary Artery; Vascular Remodeling; Severity of Illness Index; PULMONARY ARTERY; Pulmonary Disease, Chronic Obstructive; 03 medical and health sciences; Forced Expiratory Volume; https://purl.org/becyt/ford/3.1; COPD; Humans; Gene Regulatory Networks; https://purl.org/becyt/ford/3; Aged; Cell Proliferation; 0303 health sciences; Cell Differentiation; Middle Aged; 3. Good health; MicroRNAs; VASCULAR REMODELING; Gene Expression Regulation; Female; E2F1 Transcription Factor

Pulmonary vascular remodeling is an angiogenic-related process involving changes in smooth muscle cell (SMC) homeostasis, which frequently observed chronic obstructive pulmonary disease (COPD). MicroRNAs (miRNAs) are small, noncoding RNAs that regulate mRNA expression levels of many genes, leading to the manifestation identity and specific cellular phenotypes. Here, we evaluate miRNA profiles arteries (PAs) patients with COPD its relationship regulation SMC phenotypic change. from PAs 12 COPD, 9 smokers normal lung function (SK), 7 nonsmokers (NS) were analyzed using TaqMan Low-Density Arrays. In miR-98, miR-139-5p, miR-146b-5p, miR-451 upregulated, as compared NS. contrast, miR-197, miR-204, miR-485-3p, miR-627 downregulated. miRNA-197 correlated both airflow obstruction PA intimal enlargement. vitro model differentiation, miR-197 was associated contractile phenotype. inhibition blocked acquisition markers SMCs promoted a proliferative/migratory phenotype measured by cycle analysis wound-healing assay. Using luciferase assays, Western blot, quantitative PCR, confirmed targets transcription factor E2F1. E2F1 increased vessel wall downregulation regulates The effect on might be mediated, at least part, key proproliferative factor,