Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
[Preprint]. 2024 May 6:rs.3.rs-4319658.
doi: 10.21203/rs.3.rs-4319658/v1.

Renalase Levels are Decreased in Maternal Blood and Placental Tissues in Pregnancies Associated with Preterm Preeclampsia

Youstina Soliman  1   2 , Chino Eke  1 , Xiaojia Guo  1   3 , Melinda Wang  4 , Tatiana Silva  1 , Gary V Désir  1   3   5 , Liza Konnikova  1   6   7
Affiliations

Renalase Levels are Decreased in Maternal Blood and Placental Tissues in Pregnancies Associated with Preterm Preeclampsia

Youstina Soliman et al. Res Sq. .

Abstract

Preeclampsia (PEC) is a complication of pregnancy associated with hypertension and the risk of eclampsia. The pathophysiology of PEC is unknown and identifying factors associated with PEC during pregnancy is crucial for placental, fetal, and maternal health. Renalase (RNLS) is an anti-inflammatory secretory flavoprotein associated with hypertension. Recent data demonstrated a correlation between maternal serum RNLS and PEC, and work from our group identified RNLS expression in the placenta. However, it remains unknown whether RNLS levels in placenta are altered by preeclampsia. Additionally, it is unclear if there is a differential effect of preterm and term PEC on RNLS. We demonstrate that serum RNLS was reduced in preterm cases of PEC. Similarly, placental RNLS was diminished in the chorion of preterm cases of PEC. However, a reduction of RNLS in the decidua was observed with all cases of PEC, while the levels of RNLS within the placental villi were similar in all cases. Overall, we demonstrate that RNLS correlates with PEC both systemically in maternal serum and locally within the placenta, with variable effects on the different layers of the placenta and more pronounced in preterm cases.

Keywords: Maternal Serum; PEC; Placenta; Preeclampsia; RNLS; Renalase.

PubMed Disclaimer

Conflict of interest statement

Competing Interests G.D. is a named inventor on several issued patents related to the discovery and therapeutic use of renalase. Renalase is licensed to Bessor Pharma, and G.D. holds an equity position in Bessor and its subsidiary Personal Therapeutics. All other authors do not have any competing interests to disclose.

Figures

Figure 1.
Figure 1.
RNLS levels reduced in maternal serum in preterm cases with PEC. (A) ELISAs performed on 28 maternal serum samples display the RNLS abundance (ng/ml) for the native and acid sensitive fractions. (B) The ratio native RNLS to acid sensitive RNLS present in maternal serum per each cohort – PP, PNP, TP, and TNP. (C) Grouped ratio of native RNLS to acid sensitive RNLS of preterm and term samples. * Reflects a p-value < 0.05 and ** reflects a p-value < 0.01 PP – preterm preeclampsia, PNP – preterm no preeclampsia, TP – term preeclampsia, and TNP – term non preeclampsia.
Figure 2.
Figure 2.
RNLS levels compared across placental layers and elevated in placental villi. (A) The RNLS expression per high powered field comparing decidua, chorionic interstitium, chorionic trophoblasts, placental villi interstitium, and placental villi trophoblasts. ** Reflects a p-value < 0.01 and **** reflects a p-value < 0.0001.
Figure 3.
Figure 3.
RNLS levels are reduced in the decidua samples affected by PEC. (A-D) Labeling for RNLS with m28 antibodies in decidual samples. Scale bar is 110 μm. Scale bar for inset is equivalent to 22 μm. (E) The RNLS expression per high powered field comparing PP, PNP, TP, and TNP in the decidua. * Reflects a p-value < 0.05. PP – preterm preeclampsia, PNP – preterm no preeclampsia, TP – term preeclampsia, and TNP – term non preeclampsia.
Figure 4.
Figure 4.
RNLS levels are reduced in the fetal membranes of preterm samples with PEC. (A-D) Labeling for RNLS with m28 antibodies in fetal membranes samples. Scale bar is 110 μm. Scale bar for inset is 15 μm. (E) The RNLS expression per high powered field comparing PP, PNP, TP, and TNP in the chorionic interstitium. (F) The RNLS expression per high powered field comparing PP, PNP, TP, and TNP in the chorionic trophoblast. * Reflects a p-value < 0.05. PP – preterm preeclampsia, PNP – preterm no preeclampsia, TP – term preeclampsia, and TNP – term non preeclampsia.
Figure 5.
Figure 5.
Placental Villi (PV) RNLS levels are not altered by PEC. (A-D) Labeling for RNLS with m28 antibodies in PV samples at 20x. Scale bar is equivalent to 110 μm. Scale bar for inset is equivalent to 15 μm. (E) The RNLS expression per high powered field comparing PP, PNP, TP, and TNP in the placenta villi interstitium. (F) The RNLS expression per high powered field comparing PP, PNP, TP, and TNP in the placenta villi trophoblast. * Reflects a p-value < 0.05. PP – preterm preeclampsia, PNP – preterm no preeclampsia, TP – term preeclampsia, and TNP – term non preeclampsia.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Fox R, Kitt J, Leeson P, Aye CYL, Lewandowski AJ. Preeclampsia: Risk Factors, Diagnosis, Management, and the Cardiovascular Impact on the Offspring. J Clin Med. 2019;8(10):1625. doi:10.3390/jcm8101625 - DOI - PMC - PubMed
    1. Burton GJ, Redman CW, Roberts JM, Moffett A. Pre-eclampsia: pathophysiology and clinical implications. BMJ. 2019;366:l2381. doi:10.1136/bmj.l2381 - DOI - PubMed
    1. Amaral LM, Wallace K, Owens M, LaMarca B. Pathophysiology and Current Clinical Management of Preeclampsia. Curr Hypertens Rep. 2017;19(8):61. doi:10.1007/s11906-017-0757-7 - DOI - PMC - PubMed
    1. Odegård RA, Vatten LJ, Nilsen ST, Salvesen KA, Austgulen R. Preeclampsia and fetal growth. Obstet Gynecol. 2000;96(6):950–955. - PubMed
    1. Weiler J, Tong S, Palmer KR. Is Fetal Growth Restriction Associated with a More Severe Maternal Phenotype in the Setting of Early Onset Pre-Eclampsia? A Retrospective Study. PLOS ONE. 2011;6(10):e26937. doi:10.1371/journal.pone.0026937 - DOI - PMC - PubMed

Publication types

LinkOut - more resources