Pulmonary vascular remodeling is an angiogenic-related process involving changes in smooth muscle cell (SMC) homeostasis, which is frequently observed in chronic obstructive pulmonary disease (COPD). MicroRNAs (miRNAs) are small, noncoding RNAs that regulate mRNA expression levels of many genes, leading to the manifestation of cell identity and specific cellular phenotypes. Here, we evaluate the miRNA expression profiles of pulmonary arteries (PAs) of patients with COPD and its relationship with the regulation of SMC phenotypic change. miRNA expression profiles from PAs of 12 patients with COPD, 9 smokers with normal lung function (SK), and 7 nonsmokers (NS) were analyzed using TaqMan Low-Density Arrays. In patients with COPD, expression levels of miR-98, miR- 139-5p, miR-146b-5p, and miR-451 were upregulated, as compared with NS. In contrast, miR-197, miR-204, miR-485-3p, and miR-627 were downregulated. miRNA-197 expression correlated with both airflowobstruction andPAintimal enlargement. In an in vitro model of SMC differentiation, miR-197 expression was associated with an SMC contractile phenotype. miR-197 inhibition blocked the acquisition of contractile markers in SMCs and promoted a proliferative/migratory phenotypemeasured by both cell cycle analysis and wound-healing assay. Using luciferase assays, Western blot, and quantitative PCR, we confirmed that miR-197 targets the transcription factor E2F1. In PAs from patients with COPD, levels of E2F1 were increased as compared withNS. InPAs of patients with COPD, remodeling of the vesselwall is associated with downregulation of miR-197, which regulates SMC phenotype. The effect ofmiR-197 onPAsmight bemediated, at least in part, by the key proproliferative factor, E2F1. Fil: Musri, Melina Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina. Universidad de Barcelona; España Fil: Coll Bonfill, Núria. Universidad de Barcelona; España. Biomedical Research Centre Network For Respiratory Diseases; España Fil: Maron, Bradley A.. Brigham And Women's Hospital; Estados Unidos Fil: Peinado, Victor Ivo. Universidad de Barcelona; España. Biomedical Research Centre Network For Respiratory Diseases; España Fil: Wang, Rui Sheng. Brigham And Women's Hospital; Estados Unidos Fil: Altirriba, Jordi. Universidad de Ginebra; Suiza Fil: Blanco, Isabel. Universidad de Barcelona; España. Biomedical Research Centre Network For Respiratory Diseases; España Fil: Oldham, William M.. Brigham And Women's Hospital; Estados Unidos Fil: Tura Ceide, Olga. Biomedical Research Centre Network For Respiratory Diseases; España. Universidad de Barcelona; España Fil: García Lucio, Jessica. Universidad de Barcelona; España Fil: de la Cruz Thea, Benjamín Isaías. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina Fil: Meister, Gunter. Universitat Regensburg; Alemania Fil: Loscalzo, Joseph. Brigham And Women's Hospital; Estados Unidos Fil: Barberà, Joan A.. Universidad de Barcelona; España. Biomedical Research Centre Network For Respiratory Diseases; España