ArticleRespiratory research2023
Inhibition of miR-4640-5p alleviates pulmonary hypertension in chronic obstructive pulmonary disease patients by regulating nitric oxide synthase 1.
Article in Respiratory research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.
- Recent Evidences of Epigenetic Alterations in Chronic Obstructive Pulmonary Disease (COPD): A Systematic Review.International journal of molecular sciences · 2025Pooled it
- Critical role of mitochondrial dynamics in chronic respiratory diseases and new therapeutic directions.Chinese medical journal · 2025Review
- RNA-binding proteins as a molecular link between COPD and pulmonary hypertension.International journal of medical sciences · 2025Review
- Protection against cigarette smoke-induced chronic obstructive pulmonary disease via activation of the SIRT1/FoxO1 axis by targeting microRNA-132.American journal of translational research · 2024Article
- Screening COPD-Related Biomarkers and Traditional Chinese Medicine Prediction Based on Bioinformatics and Machine Learning.International journal of chronic obstructive pulmonary disease · 2024Article
- The vascular perspective on acute and chronic lung disease.The Journal of clinical investigation · 2023Review
- Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPulmonary hypertension (PH) is a devastating disease characterized by vasoconstriction and vascular remodeling, leading to right ventricular failure and death. PH is a common complication of chronic obstructive pulmonary disease (COPD). Accumulating evidence demonstrate that microRNAs participate in the pathobiology of PH in COPD patients. In this study, we aimed to evaluate the expression and function of microRNA-4640-5p (miR-4640-5p) in PH.
methodsThe mRNA and protein levels were determined by quantitative polymerase chain reaction (qPCR) and western blot, separately. Functional assays and western blot were performed to determine the effects of miR-4640-5p and NOS1 on cell growth, migration. Besides, the dual-luciferase reporter assays were used to validate miR-4640-5p and NOS1 interactions.
resultsWe found that miR-4640-5p expression was significantly higher in the lung tissues of COPD-PH patients than in the healthy controls while higher expression of miR-4640-5p was correlated with more severe COPD-PH. By using pulmonary artery smooth muscle cell (PASMC) in in vitro assays, we demonstrated that inhibition of miR-4640-5p suppressed cell proliferation and migration of PASMC via regulating mTOR/S6 signaling. Bioinformatics analysis and validation experiments revealed that nitric oxide synthase 1 (NOS1) was a direct downstream target of miR-4640-5p. Overexpression of NOS1 partially antagonized the effect of miR-4640-5p in regulating PASMC cell proliferation and migration. In addition, our findings suggested that miR-4640-5p/NOS1 axis regulated mitochondrial dynamics in PASMCs. Furthermore, in the hypoxia-induced PH rat model, inhibition of miR-4640-5p ameliorated PH with reduced right ventricular systolic pressure and Fulton index.
conclusionsmiR-4640-5p regulates PH via targeting NOS1, which provides a potential diagnostic biomarker and therapeutic target for COPD-PH patients.
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