Expression Analysis of Muscle-Specific miRNAs in Plasma-Derived Extracellular Vesicles from Patients with Chronic Obstructive Pulmonary Disease

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.

Extracellular Vesicles in Blood: Sources, Effects, and Applications

“…The connection between the liver and the circulatory system suggested the presence of EVs from the liver in blood; this was confirmed in mice and human samples, in which hepatocyte-derived EVs were detected [ 73 , 74 ]. In addition, the muscle tissue also secretes EVs and, indeed, striated muscle-specific miRNAs or myo-miRNAs have been found in human plasma EVs [ 75 , 76 ]. Moreover, EVs produced by cardiomyocytes have been identified in mice and humans, as measured by cardiac bridging integrator 1 (cBIN1)-containing particles in circulation [ 77 ].…”

“…The selection of myo-miRNAs was based on the skeletal muscle dysfunction commonly suffered by patients. Indeed, this preliminary work found that miR-206, miR-133a-5p, and miR-133a-3p were upregulated only in a subgroup of patients, named group B, which could be a relevant biomarker to discriminate group B from other groups (which are based on increasing risk and severity, from group A to D) [ 76 ]. Interestingly, a work investigating different degrees of glucose tolerance evaluated both the presence of characteristic membrane markers and miRNAs.…”

The impact of obesity on adipocyte-derived extracellular vesicles

“…However, the abundance of circulating EVs may be affected by preanalytical factors such as blood sample storage time, temperature, and anticoagulants on their secretion [98][99][100]. The tissues that secret EVs into the circulating include muscle [101], lung [102], liver [103], cardiomyocytes [104], and endothelium [105]. The adipocyte-derived EVs are also found in the human circulation [105].…”

Role of extracellular vesicles in chronic lung disease

“…Carpi et al 86 investigated the differential expression of skeletal muscle-specific miRNA cargo in EVs derived from serum of patients with COPD. Patients were grouped into four groups (A, B, C and D) relevant to disease severity by GOLD criteria.…”

“…This study found that key miRNAs were upregulated in GOLD group D compared with other groups with clinical characteristics of dyspnoea, COPD assessment test, FEV 1 and FEV 1 predicted percentage all being significantly different in this group. 86…”