The long-term outcomes of tobacco control strategies based on the cognitive intervention for smoking cessation in COPD patients.

OBJECTIVE: To evaluate the long-term efficacy of tobacco control strategies based on cognitive intervention for smoking cessation in chronic obstructive pulmonary disease (COPD) patients, and to provide basis for clinical practice. MATERIALS AND METHODS: 102 COPD patients with a long-term history of smoking from the outpatient clinic were recruited in the study. These smokers were randomly divided into intervention group and control group. The intervention group received a cognitive intervention containing individual consultation, telephone follow-ups and self-help materials, etc. The prevalence of quitting smoking, acute exacerbation (AE), lung function and survival were compared in the groups in 10 years. RESULTS: There were significant differences between the intervention group and the control group in the rate of persistent quitting smoking in half a year (17.6% vs 3.9%) (P < 0.05), the rate of quitting smoking at the 6th month (58.8% vs 33.3%) (P < 0.05). After 3 months (P < 0.01) and 6 months (P < 0.01), the difference in body weight between the intervention group and the control group was statistically significant. Intervention-group patients had fewer AE per year (P < 0.01) and higher FEV1/FVC ratio (P < 0.01) after 5-year and 10-year follow-up. Besides, the FEV1% predicted in the intervention patients was higher than that in control group after 10-year follow-up. The ages of patients in the death group were greater than those in the survival group. Death-group patients had longer smoking times, higher smoking index, and later onset of COPD symptoms. Death-group patients had lower FEV1% predicted (P < 0.05) and FEV1/FVC ratio (P < 0.01). During 10-year follow-up, 30 patient deaths were recorded (the control group: n = 48; 19 deaths, and intervention group: n = 46; 11 deaths), and patients in the control group had lower survival than those in the intervention group. (P < 0.05). CONCLUSION: The method of quitting smoking based on cognitive intervention is an effective way for COPD patients to quit smoking successfully. Quitting smoking can slower deterioration in lung function and improve the survival of COPD patients. CLINICAL TRIAL REGISTRATION NUMBER: ChiCTR2000031239 (Chinese clinical trial registry).

LncRNA-SMILR modulates RhoA/ROCK signaling by targeting miR-141 to regulate vascular remodeling in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a fatal progressive disease characterized by an increased blood pressure in the pulmonary arteries. RhoA/Rho-kinase (RhoA/ROCK) signaling activation is often associated with PAH. The purpose of this study is to investigate the role and mechanisms of long noncoding RNA (lncRNA) smooth muscle-induced lncRNA (SMILR) to activate the RhoA/ROCK pathway in PAH. SMILR, microRNA-141 (miR-141), and RhoA were identified by qRT-PCR in PAH patients' serum. 3-(4,5-Dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT), wound-healing assay, cell counting kit-8 (CCK-8) assay, and flow cytometry were performed to determine cell viability, migration, proliferation, and cell cycle in human pulmonary arterial smooth muscle cells (hPASMCs) and primary PASMCs from PAH patients. We also performed bioinformatical prediction, luciferase reporter assay, and RNA-binding protein immunoprecipitation (RIP) to assess the interaction among SMILR, miR-141, and RhoA. The RhoA/ROCK pathway and proliferation-related proteins were measured by Western blotting. Finally, we introduced the small hairpin (sh)SMILR to monocrotaline-induced PAH rat model and used the hemodynamic measurement, qRT-PCR, and immunohistochemistry to examine the therapeutic effects of shSMILR. SMILR and RhoA expression were upregulated, while miR-141 expression was downregulated in PAH patients. SMILR directly interacted with miR-141 and negatively regulated its expression. Knockdown of SMILR suppressed PASMC proliferation and migration induced by hypoxia. Furthermore, overexpression of miR-141 could inhibit the RhoA/ROCK pathway by binding to RhoA, thereby repressing cell proliferation-related signals. Knockdown of SMILR significantly inhibited the Rho/ROCK activation and vascular remodeling in monocrotaline-induced rats. Knockdown of SMILR effectively elevated miR-141 expression and in turn inhibited the RhoA/ROCK pathway to regulate vascular remodeling and reduce blood pressure in PAH.NEW & NOTEWORTHY Smooth muscle enriched long noncoding RNA (SMILR), as a long noncoding RNA (lncRNA), was increased in pulmonary arterial hypertension (PAH) patients and in vitro and in vivo models. SMILR activated RhoA/ROCK signaling by targeting miR-141 to disinhibit its downstream target RhoA. SMILR knockdown or miR-141 overexpression inhibited hypoxia-induced cell proliferation and migration via repressing RhoA/ROCK signaling in pulmonary arterial smooth muscle cells (PASMCs), which was confirmed in vivo experiments that knockdown of SMILR inhibited vascular remodeling and alleviated PAH in rats. SMILR may be a promising and novel therapeutic target for the treatment and drug development of PAH.