Longitudinal Study of the Vascular Glycocalyx and Urinary Podocyte Markers During Pregnancy

We aimed to assess the longitudinal changes of glycocalyx, a proteoglycan/glycoprotein layer that lines and protects endothelial cells in normotensive pregnancies (NPs); to correlate glycocalyx parameters with kidney injury markers (podocin-positive to nephrin-positive [P/N] ratio); and to explore c...

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Published in:Journal of the American Heart Association Vol. 14; no. 15; p. e039904
Main Authors: Garcia Valencia, Oscar, Suvakov, Sonja, Tu, Haitao, Dilmaghani, Darah, Milic, Natasa M., Weissgerber, Tracey L., Dokic, Vladimir, Gavrilovici, Paul, Hatamova, Jennet, Miao, Jing, White, Wendy M., Jayachandran, Muthuvel, Nath, Karl, Garovic, Vesna D.
Format: Journal Article
Language:English
Published: England Wiley 05.08.2025
Subjects:
Adult
Biomarkers - blood
Biomarkers - urine
Female
Glycocalyx - metabolism
Humans
Longitudinal Studies
Membrane Proteins - urine
microcirculation
nephrin
perfused boundary region
podocin
Podocytes - metabolism
Podocytes - pathology
Pre-Eclampsia - blood
Pre-Eclampsia - diagnosis
Pre-Eclampsia - metabolism
Pre-Eclampsia - urine
preeclampsia
Pregnancy
Pregnancy Trimesters - urine
syndecan 1
Syndecan-1 - blood
Young Adult
perfused boundary region
podocin
syndecan 1
nephrin
preeclampsia
microcirculation
vascular glycocalyx
ISSN:2047-9980, 2047-9980
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Summary:We aimed to assess the longitudinal changes of glycocalyx, a proteoglycan/glycoprotein layer that lines and protects endothelial cells in normotensive pregnancies (NPs); to correlate glycocalyx parameters with kidney injury markers (podocin-positive to nephrin-positive [P/N] ratio); and to explore changes in P/N ratio in preeclampsia. Plasma and urine samples and glycocalyx measurements using side-stream darkfield imaging were collected at each trimester from pregnant women (n=31). Plasma glycocalyx components were measured by ELISA, and urinary P/N-positive extracellular vesicles by flow cytometry. In NPs (n=26), glycocalyx degradation increased from the first to the second trimester ( =0.008) and returned to first-trimester values in the third trimester ( =0.008). Microvascular perfusion decreased from the first to the second trimester ( =0.006) and increased back to first-trimester values by the third trimester ( =0.039). Plasma syndecan 1 level showed a steady increase from the first to the second trimester ( <0.001) and further in the third trimester ( <0.001); hyaluronic acid increased from the first to the second trimester ( =0.016) without further changes. Glycocalyx degradation was associated with an increase in P/N ratio from the first to the second trimester of NPs and remained stable through the third trimester. P/N ratio strongly correlated with elevated syndecan 1 and hyaluronic acid levels in the third trimester. Comparison of P/N ratios between NP and preeclampsia (n=5) showed higher values in preeclampsia across all trimesters ( =0.028). Glycocalyx changes during NPs are associated with elevated urinary podocyte markers. Increase in P/N ratio across NPs, and further in preeclampsia, suggests that podocyte injury in preeclampsia is extension of physiological changes in pregnancy, which may predate its clinical presentation.
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ISSN:2047-9980
2047-9980
DOI:10.1161/JAHA.124.039904