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This phase 0 study aimed to identify biomarkers differentiating between patients with mitochondrial disease and healthy volunteers (HVs). In this cross\u2010sectional case\u2013control study, eight participants with mitochondrial disease and eight HVs matched on age, sex, and body mass index underwent study assessments consisting of blood collection for evaluation of plasma and serum biomarkers, mitochondrial function in peripheral blood mononuclear cells (PBMCs), and an array of imaging methods for assessment of (micro)circulation. Plasma biomarkers GDF\u201015, IL\u20106, NT\u2010proBNP, and cTNI were significantly elevated in patients compared to HVs, as were several clinical chemistry and hematology markers. No differences between groups were found for mitochondrial membrane potential, mitochondrial reactive oxygen production, oxygen consumption rate, or extracellular acidification rate in PBMCs. Imaging revealed significantly higher nicotinamide\u2010adenine\u2010dinucleotide\u2010hydrogen (NADH) content in skin as well as reduced passive leg movement\u2010induced hyperemia in patients. This study confirmed results of earlier studies regarding plasma biomarkers in mitochondrial disease and identified several imaging techniques that could detect functional differences at the tissue level between participants with mitochondrial disease and HVs. However, assays of mitochondrial function in PBMCs did not show differences between participants with mitochondrial disease and HVs, possibly reflecting compensatory mechanisms and heterogeneity in mutational load. In future clinical trials, using a mix of imaging and blood\u2010based biomarkers may be advisable, as well as combining these with an in vivo challenge to disturb homeostasis.<\/jats:p>","DOI":"10.1111\/cts.13530","type":"journal-article","created":{"date-parts":[[2023,5,13]],"date-time":"2023-05-13T06:39:46Z","timestamp":1683959986000},"page":"1258-1271","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Identification of peripheral vascular function measures and circulating biomarkers of mitochondrial function in patients with mitochondrial disease"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2465-1831","authenticated-orcid":false,"given":"Sebastiaan J. 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