Abstract
MicroRNAs (miRNAs) are a class of short non-coding RNAs involved in the regulation of gene expression and the control of several cellular processes at physiological and pathological levels. Furthermore, extracellular vesicles (EV), which are small membrane-bound vesicles secreted by cells in the extracellular environment, contain functional miRNAs. The remarkable deregulation of many miRNAs has been demonstrated in respiratory diseases. Among them, miR-206, miR-133a-5p, and miR-133a-3p are striated muscle-specific miRNAs (myo-miRNA), related to skeletal muscle dysfunction, one of the commonest systemic manifestations in patients with chronic obstructive pulmonary disease (COPD). Nevertheless, their circulating expression in COPD patients is not demonstrated. For these reasons, we performed a pilot study to analyze the expression profiles of myo-miRNAs in plasma-derived EV from patients with COPD. We analyzed the expression profiles of selected myo-miRNAs in plasma-derived EV from COPD. Receiver operating characteristic analyses were carried out to evaluate whether selected plasma miRNAs were able to discriminate between different groups of COPD patients. We found EV-embedded myo-miRNAs in the bloodstream of COPD patients. Specifically, miR-206, miR-133a-5p and miR-133a-3p were significantly upregulated in group B patients. Receiver operating characteristic analyses of the combination of these selected miRNAs showed their high capacity to discriminate group B from other COPD patients. Our data provide evidence that myo-miRNA are present in EV in the plasma of COPD patients and their expression (miR-206, miR-133a-5p, and miR-133a-3p) can discriminate group B from group C patients. The future analysis of a larger number of patients should allow us to obtain more refined correlations.
Highlights
Chronic obstructive pulmonary disease (COPD) is a heterogeneous and complex disease associated with significant morbidity and mortality and represents a leading cause of mortality worldwide [1].Over the last ten years, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) document has moved beyond a lung function-centered view (only based on Forced Expiratory Volume in the firstDiagnostics 2020, 10, 502; doi:10.3390/diagnostics10070502 www.mdpi.com/journal/diagnosticsDiagnostics 2020, 10, 502 second (FEV1)) towards a more comprehensive approach, including exacerbation history and symptoms
Patient Characteristics and Enumeration of extracellular vesicles (EV) According to GOLD Groups
Blood samples were collected and EV isolated from 35 chronic obstructive pulmonary disease (COPD) patients with different disease severities, classified according to GOLD 2011 guidelines [2] into four groups
Summary
Chronic obstructive pulmonary disease (COPD) is a heterogeneous and complex disease associated with significant morbidity and mortality and represents a leading cause of mortality worldwide [1].Over the last ten years, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) document has moved beyond a lung function-centered view (only based on Forced Expiratory Volume in the firstDiagnostics 2020, 10, 502; doi:10.3390/diagnostics10070502 www.mdpi.com/journal/diagnosticsDiagnostics 2020, 10, 502 second (FEV1)) towards a more comprehensive approach, including exacerbation history and symptoms. D) [2], while group A contains the mildest patients and group D, the most severe ones, establishing disease severity among groups B and C is still challenging [3] These groups, are still considered unsatisfactory to fully classify the disease for clinical and research purposes [4,5,6], since COPD represents a complex pathological condition with several important extrapulmonary manifestations (cardiovascular diseases, skeletal muscle dysfunction and subsequent deconditioning, sarcopenia, metabolic disorders, etc.) [2]. Since it is not feasible to obtain lung tissue samples from patients in clinical practice, it is not easy to obtain pathological information on the pulmonary state Biofluids such as blood, bronchoalveolar lavage fluid, and sputum represent important sources of circulating biomolecules able to give information about lung conditions
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