Early Onset Preeclampsia Is Associated With Glycocalyx Degradation and Reduced Microvascular Perfusion

Abstract

Background The endothelial glycocalyx is a vasoprotective barrier between the blood and endothelium. We hypothesized that glycocalyx degradation is present in preeclampsia, a pregnancy‐specific hypertensive disorder characterized by endothelial dysfunction and activation. Methods and Results We examined the sublingual glycocalyx noninvasively using sidestream dark field imaging in the third trimester among women with normotensive pregnancies (n=73), early (n=14) or late (n=29) onset preeclampsia, or gestational diabetes mellitus (n=21). We calculated the width of the glycocalyx that was permeable to red blood cells (called the perfused boundary region , a measure of glycocalyx degradation) and the percentage of vessels that were filled with red blood cells ≥50% of the time (a measure of microvascular perfusion). In addition, we measured circulating levels of glycocalyx components, including heparan sulfate proteoglycans, hyaluronic acid, and SDC1 (syndecan 1), in a subset of participants by ELISA . Repeated‐measures ANOVA was performed to adjust for vessel diameter and caffeine intake. Women with early onset preeclampsia showed higher glycocalyx degradation, indicated by a larger perfused boundary region (mean: 2.14 [95% CI, 2.05–2.20]), than the remaining groups (mean: normotensive: 1.99 [95% CI, 1.95–2.02], P =0.002; late‐onset preeclampsia: 2.01 [95% CI, 1.96–2.07], P =0.024; gestational diabetes mellitus: 1.97 [95% CI, 1.91–2.04], P =0.004). The percentage of vessels that were filled with red blood cells was significantly lower in early onset preeclampsia. These structural glycocalyx changes were accompanied by elevated plasma concentrations of the glycocalyx components, heparan sulfate proteoglycans and hyaluronic acid, in early onset preeclampsia compared with normotensive pregnancy. Conclusions Glycocalyx degradation and reduced microvascular perfusion are associated with endothelial dysfunction and activation and vascular injury in early onset preeclampsia.

Markers of Endothelial Injury and Dysfunction in Early- and Late-Onset Preeclampsia

“…Increased serum concentration of endothelial glycocalyx (EG) components, including hyaluronan (HA), constitutes one of the new markers of endothelial injury in PE [ 4 , 5 ]. A previous study showed that the degree of endothelial injury, expressed as the serum concentration of HA, was comparable in women with EOP and LOP [ 6 ].…”

Loss of Endothelial Glycocalyx Hyaluronan Impairs Endothelial Stability and Adaptive Vascular Remodeling after Arterial Ischemia

“…Removal of HA by hyaluronidase results in myocardial edema in perfused rat hearts [26]. Degradation of endothelial glycocalyx including HA is associated with reduced microvascular perfusion due to endothelial dysfunction and vascular injury [14,15]. High molecular weight HA enhances human pulmonary EC barrier function and inhibits LPS-induced pulmonary vascular leakiness [27].…”

“…In pathological conditions, like inflammation, hyperglycemia, and atherosclerosis, the endothelial glycocalyx is degraded by enzymes such as heparanase and hyaluronidases [11][12][13]. Such impaired endothelial glycocalyx results in endothelial dysfunction and is associated with a less efficient and defective microvascular perfusion [14,15].…”

Review of Alterations in Perlecan-Associated Vascular Risk Factors in Dementia

“…However, no change was detected in perlecan expression in a coarctation of abdominal aorta model of hypertension in rats [174]. In pregnant women, an association was found between increased plasma concentration of perlecan and early onset of gestational hypertension [175]. The authors attributed their findings to impaired microvascular perfusion leading to the degradation of glycocalyx of the kidneys.…”