8532 Circulating Neprilysin in Pregnancy

Abstract Disclosure: A. Kulovic-Sissawo: None. E. Weiss: None. E. Jantscher-Krenn: None. U. Hiden: None. Background: In the complex nature of pregnancy, the female organism undergoes pivotal vascular and metabolic changes orchestrated by a tightly regulated interplay of bioactive regulatory molecules. The neutral endopeptidase, neprilysin, exists both in a membrane-bound and a soluble form (sNEP), of with the latter present in the circulatory system. Neprilysin degrades an exciting range of bioactive peptides involved in glycemic control (insulin B chain, GLP-1) and vascular tone regulation (angiotensin I and II, bradykinin, ANP, BNP), and both of them are altered in pregnancy. Objective: Due to the substrate-specificity of neprilysin and its multifaceted role we hypothesize that neprilysin may be involved in metabolic and vascular adaptions during pregnancy. However, the link between sNEP and maternal metabolism in pregnancy has not yet been investigated. Methodology: Serum sNEP concentration (n=102), longitudinally collected from metabolically healthy women (trial number NTC05496712), was measured at three visits throughout gestation (gestational age: 12.5±0.7; 20±0.8; 33±1.6 weeks) and post-partum (2±1.2 days after delivery) using commercially available sandwich ELISA. In addition, sNEP levels in pregnancy were compared to a cohort of non-pregnant women within reproductive age (n=50). Clinical and anthropometric measurements were determined and the association of sNEP and metabolic characteristics elucidated. Results: Circulating sNEP levels were non-normally distributed (median ± IQR: 2334±232624 pg/ml, n=82, gestational age 12.5±0.7 weeks) and showed high biological variability, with individual levels remaining constant over gestation. After delivery, however, sNEP concentration decreased (median± IQR: 1968±171060 pg/ml n=82, p=0.0001). sNEP showed a positive correlation with systolic blood pressure (Spearman, n=56, r=0.321, p=0.02) at early stages of pregnancy and non-fasting GLP-1 (Spearman, n=98, r=0.309, p=0.002) throughout gestation, but not with blood glucose, insulin resistance or BMI. In the non-pregnant state sNEP concentration (median±IQR: 4322±392152 pg/ml, n=38) positively correlated with body fat percentage (Pearson, n=38, r=0.405, p=0.01), fasting glucose (Pearson, n=43, r=0.301, p=0.05) and body mass index (Spearman, n=38, r=0.369, p=0.02) but did not correlate with systolic blood pressure (Pearson, n=36, r=-0.120, p=0.48). Conclusion: For the first time, the link between sNEP, metabolism and blood pressure during uncomplicated pregnancy was investigated. The decrease in post-partum circulating sNEP as compared to levels throughout pregnancy suggests a particular way of sNEP regulation and release during gestation. Our data indicate that in both, pregnant and non-pregnant state, sNEP may be involved in metabolic and cardiovascular regulation, with circulating sNEP levels showing massive individual differences. Presentation: 6/3/2024