Exploring mitochondrial DNA copy number in circulating cell‐free DNA and extracellular vesicles across cardiovascular health status: A prospective case–control pilot study

• Published in: The FASEB journal Vol. 38; no. 10; pp. e23672 - n/a
• Main Authors: Rucci, Chiara, Simone, Gaia, Salathia, Saniya, Casadidio, Cristina, Censi, Roberta, Bordoni, Laura
• Format: Journal Article
• Language: English
• Published: United States 31.05.2024
• Subjects: Aged; Cardiovascular Diseases - blood; Cardiovascular Diseases - genetics; Case-Control Studies; Cell-Free Nucleic Acids - blood; Cell-Free Nucleic Acids - genetics; cell‐free DNA; CVD; DNA Copy Number Variations; DNA, Mitochondrial - blood; DNA, Mitochondrial - genetics; extracellular vesicles; Extracellular Vesicles - genetics; Extracellular Vesicles - metabolism; Female; heart attack; Humans; Male; Middle Aged; mitochondrial DNA; Pilot Projects; Prospective Studies; CVD; extracellular vesicles; heart attack; mitochondrial DNA; cell‐free DNA
• ISSN: 0892-6638; 1530-6860
• DOI: 10.1096/fj.202400463R

Cardiovascular disease (CVD) is a leading global cause of mortality, difficult to predict in advance. Evidence indicates that the copy number of mitochondrial DNA (mtDNAcn) in blood is altered in individuals with CVD. MtDNA released into circulation may act as a mediator of inflammation, a recognized factor in the development of CVD, in the long distance. This pilot study aims to test if levels of mtDNAcn in buffy coat DNA (BC‐mtDNA), in circulating cellfree DNA (cf‐mtDNA), or in DNA extracted from plasma extracellular vesicles (EV‐mtDNA) are altered in CVD patients and if they can predict heart attack in advance. A group of 144 people with different CVD statuses (50 that had CVD, 94 healthy) was selected from the LifeLines Biobank according to the incidence of new cardiovascular event monitored in 6 years (50 among controls had heart attack after the basal assessment). MtDNAcn was quantified in total cf‐DNA and EV‐DNA from plasma as well as in buffy coat. EVs have been characterized by their size, polydispersity index, count rate, and zeta potential, by Dynamic Light Scattering. BC‐mtDNAcn and cf‐mtDNAcn were not different between CVD patients and healthy subjects. EVs carried higher mtDNAcn in subject with a previous history of CVD than controls, also adjusting the analysis for the EVs derived count rate. Despite mtDNAcn was not able to predict CVD in advance, the detection of increased EV‐mtDNAcn in CVD patients in this pilot study suggests the need for further investigations to determine its pathophysiological role in inflammation. Mitochondrial DNA copy number (mtDNAcn) in buffy coat or total cell‐free DNA fraction is not associated to cardiovascular health in this cohort. In contrast, mtDNAcn measured in plasma extracellular vesicles (EV‐mtDNAcn) is higher in cardiovascular disease patients than controls. This evidence suggests that variations in EV‐mtDNAcn may offer more insights into cardiovascular health compared to total cell‐free DNA fraction. None of the biomarkers related to mtDNAcn was able to predict heart attack in advance.