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 airflow obstruction and PA intimal 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 phenotype measured 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 with NS. In PAs of patients with COPD, remodeling of the vessel wall is associated with downregulation of miR-197, which regulates SMC phenotype. The effect of miR-197 on PAs might be mediated, at least in part, by the key proproliferative factor, E2F1.

Vascular smooth muscle cells (SMC) are a highly specialized cell type that exhibit extraordinary plasticity in adult animals in response to a number of environmental cues. Upon vascular injury, SMC undergo phenotypic switch from a contractile-differentiated to a proliferative/migratory-dedifferentiated phenotype. This process plays a major role in vascular lesion formation and during the development of vascular remodeling. Vascular remodeling comprises the accumulation of dedifferentiated SMC in the intima of arteries and is central to a number of vascular diseases such as arteriosclerosis, chronic obstructive pulmonary disease or pulmonary hypertension. Therefore, it is critical to understand the molecular mechanisms that govern SMC phenotype. In the last decade, a number of new classes of noncoding RNAs have been described. These molecules have emerged as key factors controlling tissue homeostasis during physiological and pathological conditions. In this review, we will discuss the role of noncoding RNAs, including microRNAs and long noncoding RNAs, in the regulation of SMC plasticity.