Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease (Aug 2025)

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

  • Oscar Garcia Valencia,
  • Sonja Suvakov,
  • Haitao Tu,
  • Darah Dilmaghani,
  • Natasa M. Milic,
  • Tracey L. Weissgerber,
  • Vladimir Dokic,
  • Paul Gavrilovici,
  • Jennet Hatamova,
  • Jing Miao,
  • Wendy M. White,
  • Muthuvel Jayachandran,
  • Karl Nath,
  • Vesna D. Garovic

DOI
https://doi.org/10.1161/jaha.124.039904
Journal volume & issue
Vol. 14, no. 15

Abstract

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Background 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. Methods 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. Results In NPs (n=26), glycocalyx degradation increased from the first to the second trimester (P=0.008) and returned to first‐trimester values in the third trimester (P=0.008). Microvascular perfusion decreased from the first to the second trimester (P=0.006) and increased back to first‐trimester values by the third trimester (P=0.039). Plasma syndecan 1 level showed a steady increase from the first to the second trimester (P<0.001) and further in the third trimester (P<0.001); hyaluronic acid increased from the first to the second trimester (P=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 (P=0.028). Conclusions 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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