MOTS-c is associated with oxidative stress and arterial stiffness in peritoneal dialysis patients: a pilot study.
This pilot observational study investigated the relationship between MOTS-c — a mitochondria-derived peptide — and cardiovascular risk markers in 32 stable peritoneal dialysis (PD) patients (mean age ~61 years, ~63% male). Researchers measured MOTS-c in three compartments: serum, urine, and peritoneal dialysate. Oxidative stress was assessed via plasma Advanced Oxidation Protein Products (AOPPs), and vascular stiffness was evaluated using carotid-femoral Pulse Wave Velocity (PWV), with echocardiography used to assess left ventricular systolic function. The study found that urinary MOTS-c was inversely correlated with AOPPs (suggesting a link to lower oxidative stress) and positively associated with PWV and left ventricular systolic function. Dialysate MOTS-c showed a strong inverse correlation with PWV and with both systolic and diastolic blood pressure, suggesting an association with a more favorable vascular profile. The authors propose a novel "Mitochondrial-Vascular Axis" in uremia and position MOTS-c as a potential biomarker. Key limitations include the very small sample size (n=32), pilot/cross-sectional design, single-center recruitment, and inability to establish causality from correlational data.
Why this grade: While conducted in humans, the study is a small (n=32) single-center pilot with a cross-sectional, correlational design, precluding causal inference or generalizability.
Purpose Oxidative stress (OS) and endothelial dysfunction are major drivers of cardiovascular disease (CVD) in peritoneal dialysis (PD). MOTS-c, a mitochondria-derived peptide, is emerging as a key regulator of skeletal muscle health, metabolic homeostasis, and vascular function, yet its role in the uremic environment remains unexplored. We investigated the relationship between MOTS-c levels, OS markers, and vascular stiffness in PD patients. Methods This pilot, clinical study included 32 stable PD patients (mean age 60.7 ± 1.2 years, 62.5% male). MOTS-c levels were quantified in serum (sMOTS-c), urine (uMOTS-c), and peritoneal dialysate (dMOTS-c). Systemic oxidative status was assessed via plasma Advanced Oxidation Protein Products (AOPPs). Vascular function was evaluated by carotid-femoral Pulse Wave Velocity (PWV), and left ventricular systolic function was assessed echocardiographically. Results Urinary MOTS-c (uMOTS-c) levels were inversely correlated with serum AOPPs (R = - 0.592, p = 0.012) and a positive association with PWV (R = 0.708, p = 0.001) and left ventricular systolic function (R = 0.440, p = 0.04). Conversely, dialysate MOTS-c (dMOTS-c) were strongly and inversely correlated with PWV (R = - 0.717, p = 0.019) as well as systolic and diastolic blood pressure (R = -0.5, p Conclusion Ηigher urinary MOTS-c was linked to lower systemic oxidative stress, suggesting a potential protective role, and associated with greater arterial stiffness, potentially reflecting a compensatory response to vascular injury. In contrast, higher peritoneal MOTS-c levels were associated with an improved vascular profile. These findings suggest a novel 'Mitochondrial-Vascular Axis' in uremia, highlighting MOTS-c as a potential biomarker.
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