Microvascular Endothelial Glycocalyx Function in Human Pregnancy and Postpartum in Women with a History of Preeclampsia

Abstract

Preeclampsia (PreE) is a cardiovascular disorder of late pregnancy characterized by de novo hypertension and multi‐organ dysfunction. PreE occurs in 5–8% of all pregnancies and is associated with impaired microvascular endothelial function that promotes progression of the disease. The glycocalyx layer protects the endothelium from leukocyte and platelet adhesion but becomes damaged with aging and cardiovascular disease. However, whether it is altered during healthy pregnancy and/or PreE is unknown. The purpose of this study was to determine 1) the temporal change in glycocalyx across trimesters and postpartum in healthy pregnancy, and 2) whether alterations in glycocalyx layer thickness occurs postpartum in women with a history of PreE. Hematocrit (Hct) and endothelial glycocalyx thickness was assessed by perfused boundary region (PBR5‐25) and red blood cell (RBC) filling percent using Sideview Dark Field imaging (Glycocheck). PBR5‐25 (larger indicates less glycocalyx thickness) and RBC Filling % (lower indicates less vessel RBC perfused) were measured in sublingual microvessels in 1st (n=56), 2nd (n=56), 3rd (n=56) trimester of pregnancy, and 12 weeks postpartum (n=51) in a longitudinal cohort. PBR5‐25 was significantly higher in 2nd and 3rd trimester (2.10 ± 0.03 and 2.12 ± 0.03 uM) compared with the 1st trimester (2.02 ± 0.03 uM, both P<0.05), but was significantly lower 12 weeks postpartum compared with the 2nd and 3rd trimesters (both P<0.001). RBC Filling % was significantly reduced in the 2nd and 3rd trimesters (0.70 ± 0.01 and 0.71 ± 0.01%) compared with the 1st trimester (0.73 ± 0.01%, both P<0.05), but was significantly higher 12 weeks postpartum compared with the 2nd and 3rd trimesters (both P<0.01). Hct was inversely correlated with PBR5‐25 in the 1st, 2nd, 3rd trimesters and 12 weeks postpartum (r= −0.36 to −0.51, all P<0.05). In a separate cross‐sectional cohort at 1–3 years postpartum (n=38), Hct, PBR5‐25 and RBC Filling % were assessed in women with history of PreE (n=19) or healthy pregnancy (n=19). In the cross‐sectional cohort, PRB5‐25 was significantly lower (1.96 ± 0.05 vs. 2.13 ± 0.06 uM, P<0.05) and RBC Filling was significantly higher (0.75 ± 0.01 vs. 0.70 ± 0.01%, P<0.01) among PreE compared with healthy pregnancy. At 1–3 years postpartum, Hct did not differ between groups (P=0.47) and was inversely associated with PBR5‐25 in the healthy controls (r= −0.71, P<0.01) but not PreE (r= 0.12, P=0.64). In conclusion, microvascular endothelial glycocalyx thickness appears to become paradoxically less across trimesters of healthy pregnancy, however volume expansion in normal pregnancy indicated by reduced Hct may have influenced the glycocalyx layer. Glycocalyx thickness appears to be altered postpartum in women with a history of PreE compared with healthy controls, but the mechanisms contributing to differential glycocalyx function postpartum in PreE will require further study.Support or Funding InformationAHA grants 15SFRN23760002 and 18SCG34350001; and University of Iowa ICRU fellowship