Circulating levels of mitochondrial oxidative stress-related peptides MOTS-c and Romo1 in stable COPD: A cross-sectional study

Abstract

BackgroundMOTS-c and Romo1 are mitochondrial peptides that are modulated by oxidative stress. No previous studies have explored circulating levels of MOTS-c in patients with chronic obstructive pulmonary disease (COPD).MethodsWe enrolled 142 patients with stable COPD and 47 smokers with normal lung function in an observational cross-sectional study. We assessed serum levels of both MOTS-c and Romo1 and associated these findings with clinical characteristics of COPD.ResultsCompared with smokers with normal lung function, patients with COPD had lower levels of MOTS-c (p = 0.02) and higher levels of Romo1 (p = 0.01). A multivariate logistic regression analysis revealed that above-median MOTS-c levels were positively associated with Romo1 levels (OR 1.075, 95% CI 1.005–1.150, p = 0.036), but no association was found with other COPD characteristics. Below-median levels of circulating MOTS-c were associated with oxygen desaturation (OR 3.25 95% CI 1.456–8.522, p = 0.005) and walking <350 meters (OR 3.246 95% CI 1.229–8.577, p = 0.018) in six-minute walk test. Above-median levels of Romo1 were positively associated with current smoking (OR 2.756, 95% CI 1.133–6.704, p = 0.025) and negatively associated with baseline oxygen saturation (OR 0.776 95% CI 0.641–0.939, p = 0.009).ConclusionsReduced levels of circulating MOTS-c and increased levels of Romo1 were detected in patients diagnosed with COPD. Low levels of MOTS-c were associated with oxygen desaturation and poorer exercise capacity using 6 min walk test. Romo1 was associated with current smoking and baseline oxygen saturation.Trial registrationwww.clinicaltrials.gov; No.: NCT04449419; URL: www.clinicaltrials.gov. Date of registration: June 26, 2020.

Alterations in circulating mitochondrial signals at hospital admission for COPD exacerbation

“…ROC curve analysis was performed in MEDCALC version 11.6.1.0 (MedCalc Software, Mariakerke, Belgium). Evaluation of HN, GDF15, MOTS-c, FGF-21 and Romo1 as dichotomized variables, with a cut-off at the median, resulted in the best discriminative power, as reported in our previous studies 22 , 23 and other similar studies. 24 , 28 We evaluated cross-sectional associations with high versus low circulating mitochondrial peptides through logistic regression with re-hospitalization as the outcome variable.…”

“…Previously, we demonstrated that MOTS-c levels are diminished in SCOPD. 23 Here, we showed that these levels are even lower in ECOPD than SCOPD. Furthermore, GDF15 and MOTS-c levels were negatively correlated, indicating that GDF15 and MOTS-c show opposite responses.…”

“…In previous studies, 22 , 23 we measured the serum levels of mitochondrial peptides in SCOPD. HN, GDF15 and Romo 1 levels in COPD patients were higher than those in smokers without COPD, MOTS-c levels were lower, and FGF21 levels did not differ.…”

“… 21 Previous studies have shown that mitochondrial peptides are altered in stable COPD (SCOPD), and are associated with several COPD characteristics. 22 , 23 To date, no studies have evaluated the circulating levels of these proteins in the setting of ECOPD.…”