A mitochondrial regulator protein, MNRR1, is elevated in the maternal blood of women with preeclampsia
Issued Date
2024-01-01
Resource Type
ISSN
14767058
eISSN
14764954
Scopus ID
2-s2.0-85182398764
Pubmed ID
38220225
Journal Title
Journal of Maternal-Fetal and Neonatal Medicine
Volume
37
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Journal of Maternal-Fetal and Neonatal Medicine Vol.37 No.1 (2024)
Suggested Citation
Suksai M., Romero R., Bosco M., Gotsch F., Jung E., Chaemsaithong P., Tarca A.L., Gudicha D.W., Gomez-Lopez N., Arenas-Hernandez M., Meyyazhagan A., Grossman L.I., Aras S., Chaiworapongsa T. A mitochondrial regulator protein, MNRR1, is elevated in the maternal blood of women with preeclampsia. Journal of Maternal-Fetal and Neonatal Medicine Vol.37 No.1 (2024). doi:10.1080/14767058.2023.2297158 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/96010
Title
A mitochondrial regulator protein, MNRR1, is elevated in the maternal blood of women with preeclampsia
Author's Affiliation
Ramathibodi Hospital
College of Engineering
Inje University Paik Hospital
Azienda Ospedaliera Universitaria Integrata Verona
University of Michigan Medical School
Michigan State University
Faculty of Medicine, Prince of Songkla University
Wayne State University School of Medicine
National Institute of Child Health and Human Development (NICHD)
Università degli Studi di Perugia
College of Engineering
Inje University Paik Hospital
Azienda Ospedaliera Universitaria Integrata Verona
University of Michigan Medical School
Michigan State University
Faculty of Medicine, Prince of Songkla University
Wayne State University School of Medicine
National Institute of Child Health and Human Development (NICHD)
Università degli Studi di Perugia
Corresponding Author(s)
Other Contributor(s)
Abstract
Objective: Preeclampsia, one of the most serious obstetric complications, is a heterogenous disorder resulting from different pathologic processes. However, placental oxidative stress and an anti-angiogenic state play a crucial role. Mitochondria are a major source of cellular reactive oxygen species. Abnormalities in mitochondrial structures, proteins, and functions have been observed in the placentae of patients with preeclampsia, thus mitochondrial dysfunction has been implicated in the mechanism of the disease. Mitochondrial nuclear retrograde regulator 1 (MNRR1) is a newly characterized bi-organellar protein with pleiotropic functions. In the mitochondria, this protein regulates cytochrome c oxidase activity and reactive oxygen species production, whereas in the nucleus, it regulates the transcription of a number of genes including response to tissue hypoxia and inflammatory signals. Since MNRR1 expression changes in response to hypoxia and to an inflammatory signal, MNRR1 could be a part of mitochondrial dysfunction and involved in the pathologic process of preeclampsia. This study aimed to determine whether the plasma MNRR1 concentration of women with preeclampsia differed from that of normal pregnant women. Methods: This retrospective case–control study included 97 women with preeclampsia, stratified by gestational age at delivery into early (<34 weeks, n = 40) and late (≥34 weeks, n = 57) preeclampsia and by the presence or absence of placental lesions consistent with maternal vascular malperfusion (MVM), the histologic counterpart of an anti-angiogenic state. Women with an uncomplicated pregnancy at various gestational ages who delivered at term served as controls (n = 80) and were further stratified into early (n = 25) and late (n = 55) controls according to gestational age at venipuncture. Maternal plasma MNRR1 concentrations were determined by an enzyme-linked immunosorbent assay. Results: 1) Women with preeclampsia at the time of diagnosis (either early or late disease) had a significantly higher median (interquartile range, IQR) plasma MNRR1 concentration than the controls [early preeclampsia: 1632 (924–2926) pg/mL vs. 630 (448–4002) pg/mL, p =.026, and late preeclampsia: 1833 (1441–5534) pg/mL vs. 910 (526–6178) pg/mL, p =.021]. Among women with early preeclampsia, those with MVM lesions in the placenta had the highest median (IQR) plasma MNRR1 concentration among the three groups [with MVM: 2066 (1070–3188) pg/mL vs. without MVM: 888 (812–1781) pg/mL, p =.03; and with MVM vs. control: 630 (448–4002) pg/mL, p =.04]. There was no significant difference in the median plasma MNRR1 concentration between women with early preeclampsia without MVM lesions and those with an uncomplicated pregnancy (p =.3). By contrast, women with late preeclampsia, regardless of MVM lesions, had a significantly higher median (IQR) plasma MNRR1 concentration than women in the control group [with MVM: 1609 (1392–3135) pg/mL vs. control: 910 (526–6178), p =.045; and without MVM: 2023 (1578–8936) pg/mL vs. control, p =.01]. Conclusions: MNRR1, a mitochondrial regulator protein, is elevated in the maternal plasma of women with preeclampsia (both early and late) at the time of diagnosis. These findings may reflect some degree of mitochondrial dysfunction, intravascular inflammation, or other unknown pathologic processes that characterize this obstetrical syndrome.