Altered serum soluble furin and prorenin receptor levels in pregnancies with pre-eclampsia and fetal growth restriction - 18/07/21

Doi : 10.1016/j.jogoh.2021.102198

Akiko Ohwaki ^a,^b, Haruki Nishizawa ^a,^⁎ , Asuka Kato ^a, Hikari Yoshizawa ^a,^b, Jun Miyazaki ^a,^b, Yoshiteru Noda ^a,^b, Yoshiko Sakabe ^a,^b, Takao Sekiya ^a, Takuma Fujii ^a, Hiroki Kurahashi ^b
^a Department of Obstetrics and Gynecology, Fujita Health University School of Medicine, Toyoake, Japan
^b Division of Molecular Genetics, Institute for Comprehensive Medical Science, Fujita Health University, Toyoake, Japan

^⁎Correspondence and request for reprints should be addressed to: Haruki Nishizawa, Department of Obstetrics and Gynecology, Fujita Health University, 1-98 Dengakugakubo, Kutsukake, Toyoake, Aichi, 470-1192 Japan, Phone: +81-562-93-9294, Fax: +81-562-95-1821Department of Obstetrics and GynecologyFujita Health University1-98 Dengakugakubo KutsukakeToyoakeAichi470-1192Japan

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Abstract

Objective

: The proprotein convertase furin is known to be involved in the processing of pro-B-type natriuretic peptide (proBNP) and prorenin receptor (PRR), suggesting that it has a potential function in blood pressure regulation. We investigated the role of furin in the etiology of pre-eclampsia and its related disorder, unexplained fetal growth restriction (FGR) without hypertension.

Methods

: We evaluated serum and placental furin levels in pre-eclampsia, FGR and uncomplicated pregnancy. Additionally, we investigated the correlation between the serum furin levels and products of furin enzymatic activity or clinical parameters.

Results

: We demonstrated that the maternal circulation in cases of pre-eclampsia and FGR had lower levels of soluble furin than uncomplicated pregnancies. Both NT-proBNP and soluble PRR were elevated in pre-eclampsia, whereas only soluble PRR was at higher levels in unexplained FGR. Linear regression analysis revealed a negative correlation between the serum furin level and that of NT-proBNP or soluble PRR. While we observed that the serum furin or soluble PRR level correlated with blood pressure, a stronger correlation was observed with birth and placental weights. Further to this, the FURIN mRNA levels were significantly reduced in placental pre-eclamptic placentas as well as in FGR cases.

Conclusion

: These data suggest the possibility that reduced levels of furin may be the result of a negative feedback from the activation of the renin-angiotensin pathway that leads to feto-placental dysfunction with or without maternal hypertension. This may represent an etiologic pathway of pre-eclampsia and unexplained FGR.

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Keywords : furin, pre-eclampsia, fetal growth restriction, prorenin receptor, NT-proBNP