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•sGPVI, a platelet-derived blood biomarker, is predictive of AAAs, with high specificity in distinguishing patients with rapidly growing AAA.•Blockade of GPVI in mice with established aneurysms reduces AAA progression and mortality, indicating therapeutic potential.

Circulating cell-free mitochondrial DNA (ccf-mtDNA) may induce systemic inflammation, a common condition chronic kidney disease (CKD), by acting as a damaged-associated molecular pattern. We hypothesized that in patients with moderate to severe CKD, aerobic exercise would reduce ccf-mtDNA levels. We performed a post hoc analysis of a multicenter randomized trial (NCT01150851), measuring plasma concentrations of ccf-mtDNA at baseline and two and four months after aerobic exercise and caloric restriction. A total of 99 participants had baseline ccf-mtDNA, and 92 completed the study. The median age was 57 years, 44% were female, 23% had diabetes, and 92% had hypertension. After adjusting for demographics, blood pressure, BMI, diabetes, and eGFR, median ccf-mtDNA concentrations at baseline, two, and four months were 3.62, 3.08, 2.78 picomolar for the usual activity group, and 2.01, 2.20, 2.67 picomolar for the aerobic exercise group, respectively. A 16.1% greater increase per month in ccf-mtDNA was seen in aerobic exercise versus usual activity (p = 0.024) that was more pronounced with the combination of aerobic exercise and caloric restriction (29.5% greater increase per month). After four months of intervention, ccf-mtDNA increased in the aerobic exercise group by 81.6% (95% confidence intervals [CI] 8.2-204.8; p = 0.024) compared to usual activity and was more marked in the aerobic exercise and caloric restriction group (181.7% increase, 95% CI 41.1-462.2; p = 0.003). There was no statistically significant correlation between markers of oxidative stress and inflammation with ccf-mtDNA. Our data indicate that aerobic exercise increased ccf-mtDNA levels in patients with moderate-to-severe CKD.