Reduced Maternal Circulating Cell-Free Mitochondrial DNA Is Associated With the Development of Preeclampsia

Spencer C Cushen; Contessa A Ricci; Jessica L Bradshaw; Talisa Silzer; Alexandra Blessing; Jie Sun; Zhengyang Zhou; Sabrina M Scroggins; Mark K Santillan; Donna A Santillan; Nicole R Phillips; Styliani Goulopoulou

doi:10.1161/JAHA.121.021726

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Reduced Maternal Circulating Cell-Free Mitochondrial DNA Is Associated With the Development of Preeclampsia

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Reduced Maternal Circulating Cell-Free Mitochondrial DNA Is Associated With the Development of Preeclampsia

Spencer C Cushen, Contessa A Ricci, Jessica L Bradshaw, Talisa Silzer, Alexandra Blessing, Jie Sun, Zhengyang Zhou, Sabrina M Scroggins, Mark K Santillan, Donna A Santillan, …

Journal of the American Heart Association, Vol.11(2), pp.e021726-e021726

01/18/2022

DOI: 10.1161/JAHA.121.021726

PMCID: PMC9238514

PMID: 35014857

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Abstract

Background Circulating cell-free mitochondrial DNA (ccf-mtDNA) is a damage-associated molecular pattern that reflects cell stress responses and tissue damage, but little is known about ccf-mtDNA in preeclampsia. The main objectives of this study were to determine (1) absolute concentrations of ccf-mtDNA in plasma and mitochondrial DNA content in peripheral blood mononuclear cells and (2) forms of ccf-mtDNA transport in blood from women with preeclampsia and healthy controls. In addition, we sought to establish the association between aberrance in circulating DNA-related metrics, including ccf-mtDNA and DNA clearance mechanisms, and the clinical diagnosis of preeclampsia using bootstrapped penalized logistic regression. Methods and Results Absolute concentrations of ccf-mtDNA were reduced in plasma from women with preeclampsia compared with healthy controls ( ≤0.02), while mtDNA copy number in peripheral blood mononuclear cells did not differ between groups ( >0.05). While the pattern of reduced ccf-mtDNA in patients with preeclampsia remained, DNA isolation from plasma using membrane lysis buffer resulted in 1000-fold higher ccf-mtDNA concentrations in the preeclampsia group ( =0.0014) and 430-fold higher ccf-mtDNA concentrations in the control group ( <0.0001). Plasma from women with preeclampsia did not induce greater Toll-like receptor-9-induced nuclear factor kappa-light-chain enhancer of activated B cells-dependent responses in human embryonic kidney 293 cells overexpressing the human gene ( >0.05). Penalized regression analysis showed that women with preeclampsia were more likely to have lower concentrations of ccf-mtDNA as well as higher concentrations of nuclear DNA and DNase I compared with their matched controls. Conclusions Women with preeclampsia have aberrant circulating DNA dynamics, including reduced ccf-mtDNA concentrations and DNA clearance mechanisms, compared with gestational age-matched healthy pregnant women.

Cell-Free Nucleic Acids - genetics

DNA, Mitochondrial - genetics

Female

Humans

Leukocytes, Mononuclear

Mitochondria - genetics

Pre-Eclampsia - diagnosis

Pre-Eclampsia - genetics

Pregnancy

Details

Title: Subtitle: Reduced Maternal Circulating Cell-Free Mitochondrial DNA Is Associated With the Development of Preeclampsia
Creators: Spencer C Cushen - University of North Texas Health Science Center
Contessa A Ricci - University of North Texas Health Science Center
Jessica L Bradshaw - University of North Texas Health Science Center
Talisa Silzer - University of North Texas Health Science Center
Alexandra Blessing - University of North Texas Health Science Center
Jie Sun - University of North Texas Health Science Center
Zhengyang Zhou - University of North Texas Health Science Center
Sabrina M Scroggins - University of Iowa
Mark K Santillan - Roy J. and Lucille A. Carver College of Medicine
Donna A Santillan - Roy J. and Lucille A. Carver College of Medicine
Nicole R Phillips - University of North Texas Health Science Center
Styliani Goulopoulou - University of North Texas Health Science Center
Resource Type: Journal article
Publication Details: Journal of the American Heart Association, Vol.11(2), pp.e021726-e021726
DOI: 10.1161/JAHA.121.021726
PMID: 35014857
PMCID: PMC9238514
NLM abbreviation: J Am Heart Assoc
ISSN: 2047-9980
eISSN: 2047-9980
Grant note: UL1 TR002537 / NCATS NIH HHS T32 AG020494 / NIA NIH HHS
Language: English
Date published: 01/18/2022
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9984318322302771

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