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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| Veröffentlicht in: | Journal of the American Heart Association Jg. 14; H. 15; S. e039904 |
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| Format: | Journal Article |
| Sprache: | Englisch |
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05.08.2025
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| ISSN: | 2047-9980, 2047-9980 |
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| Abstract | 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. |
|---|---|
| AbstractList | 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. 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. 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.BACKGROUNDWe 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.METHODSPlasma 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 (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).RESULTSIn 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).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.CONCLUSIONSGlycocalyx 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. |
| Author | Suvakov, Sonja Dilmaghani, Darah Dokic, Vladimir Gavrilovici, Paul Tu, Haitao White, Wendy M. Nath, Karl Weissgerber, Tracey L. Jayachandran, Muthuvel Garovic, Vesna D. Milic, Natasa M. Garcia Valencia, Oscar Hatamova, Jennet Miao, Jing |
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| Cites_doi | 10.1002/ijgo.12802 10.1161/ATVBAHA.119.313399 10.1155/2012/586578 10.1016/j.ekir.2019.03.012 10.1093/ndt/gfl711 10.2215/cjn.12081115 10.1002/pri.66 10.2215/CJN.08160813 10.1371/journal.pone.0055399 10.1681/asn.2016111202 10.1371/journal.pone.0157608 10.3389/fphys.2022.1022770 10.1016/j.kint.2016.01.012 10.1016/j.jacc.2020.03.028 10.1016/j.ijcard.2013.07.166 10.1186/s13049-016-0239-y 10.1016/j.mvr.2010.06.005 10.1016/j.ajog.2020.08.045 10.1152/ajprenal.00532.2014 10.1016/S1470-0328(03)02962-8 10.17504/protocols.io.be5ejg3e 10.1161/CIRCULATIONAHA.106.684852 10.1371/journal.pone.0096477 10.1159/000348854 10.1097/AOG.0b013e3181a45b25 10.1177/1933719112453508 10.1161/JAHA.118.010647 10.1186/s13293-015-0021-2 10.1016/j.mvr.2013.08.007 10.3233/CH-190581 10.1097/aog.0000000000003891 10.1681/ASN.2011121181 10.1097/01.Asn.0000039661.06947.Fd 10.1038/nrneph.2013.78 |
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| SubjectTerms | 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 |
| Title | Longitudinal Study of the Vascular Glycocalyx and Urinary Podocyte Markers During Pregnancy |
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