Investigating the Effects of Atrial Natriuretic Peptide on the Maternal Endothelium to Determine Potential Implications for Preeclampsia

Author:

Binder Natalie K.123ORCID,Beard Sally123,de Alwis Natasha123ORCID,Fato Bianca R.123ORCID,Nguyen Tuong-Vi234,Kaitu’u-Lino Tu’uhevaha J.234,Hannan Natalie J.123

Affiliation:

1. Therapeutics Discovery and Vascular Function in Pregnancy Laboratory, Heidelberg, VIC 3084, Australia

2. Department of Obstetrics and Gynaecology, University of Melbourne, Heidelberg, VIC 3084, Australia

3. Mercy Perinatal, Mercy Hospital for Women, Heidelberg, VIC 3084, Australia

4. Diagnostics Discovery and Reverse Translation Laboratory, Heidelberg, VIC 3084, Australia

Abstract

Preeclampsia is associated with an increased lifelong risk of cardiovascular disease (CVD). It is not clear whether this is induced by persistent systemic organ and vascular damage following preeclampsia or due to a predisposition to both conditions that share cardiovascular pathophysiology. Common to both CVD and preeclampsia is the dysregulation of corin and its proteolytic product, atrial natriuretic peptide (ANP). ANP, a hypotensive hormone converted from pro-ANP by corin, is involved in blood pressure homeostasis. While corin is predominantly a cardiac enzyme, both corin and pro-ANP are significantly upregulated in the gravid uterus and dysregulated in preeclampsia. Relatively little is known about ANP function in the endothelium during a pregnancy complicated by preeclampsia. Here, we investigated the effect of ANP on endothelial cell proliferation and migration, markers of endothelial dysfunction, and receptor expression in omental arteries exposed to circulating preeclamptic toxins. ANP receptor expression is significantly upregulated in preeclamptic vasculature but not because of exposure to preeclampsia toxins tumour necrosis factor α or soluble fms-like tyrosine kinase-1. The supplementation of endothelial cells with ANP did not promote proliferation or migration, nor did ANP improve markers of endothelial dysfunction. The role of ANP in preeclampsia is unlikely to be via endothelial pathways.

Funder

The National Health Medical Research Council

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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1. Metabolic theory of preeclampsia: implications for maternal cardiovascular health;American Journal of Physiology-Heart and Circulatory Physiology;2024-09-01

2. Natriuretic Peptide Signaling in Uterine Biology and Preeclampsia;International Journal of Molecular Sciences;2023-08-01

3. Natriuretic peptide biomarkers in the imminent development of preeclampsia;Frontiers in Cardiovascular Medicine;2023-07-24

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