Measuring endothelial glycocalyx dimensions in humans: a potential novel tool to monitor vascular vulnerability

Abstract

The endothelial glycocalyx is increasingly considered as an intravascular compartment that protects the vessel wall against pathogenic insults. The purpose of this study was to translate an established experimental method of estimating capillary glycocalyx dimension into a clinically useful tool and to assess its reproducibility in humans. We first evaluated by intravital microscopy the relation between the distance between the endothelium and erythrocytes, as a measure of glycocalyx thickness, and the transient widening of the erythrocyte column on glycocalyx compression by passing leukocytes in hamster cremaster muscle capillaries. We subsequently assessed sublingual microvascular glycocalyx thickness in 24 healthy men using orthogonal polarization spectral imaging. In parallel, systemic glycocalyx volume (using a previously published tracer dilution technique) as well as cardiovascular risk profiles were assessed. Estimates of microvascular glycocalyx dimension from the transient erythrocyte widening correlated well with the size of the erythrocyte-endothelium gap (r = 0.63). Measurements in humans were reproducible (0.58 +/- 0.16 and 0.53 +/- 0.15 microm, coefficient of variance 15 +/- 5%). In univariate analysis, microvascular glycocalyx thickness significantly correlated with systemic glycocalyx volume (r = 0.45), fasting plasma glucose (r = 0.43), and high-density lipoprotein-cholesterol (r = 0.40) and correlated negatively with low-density lipoprotein-cholesterol (r = -0.41) as well as body mass index (r = -0.45) (all P < 0.05). In conclusion, the dimension of the endothelial glycocalyx can be measured reproducibly in humans and is related to cardiovascular risk factors. It remains to be tested whether glycocalyx dimension can be used as an early marker of vascular damage and whether therapies aimed at glycocalyx repair can protect the vasculature against pathogenic challenges.

Partial recovery of the endothelial glycocalyx upon rosuvastatin therapy in patients with heterozygous familial hypercholesterolemia

“…Thickness of endothelial glycocalyx in individual capillary blood vessels was measured by orthogonal polarization spectral (OPS) imaging of the sublingual microcirculation (Cytometrics, Philadelphia, PA) (18). Briefly, the width of flowing erythrocytes was measured in five individual capillaries before and immediately after leukocyte passage.…”

Role of the Vascular Wall in Sodium Homeostasis and Salt Sensitivity

“…27 These calculations are on the basis of in vitro experiments and most likely Current methods to measure ESL dimension in humans comprise measurement of shedding products in plasma, noninvasive side stream dark-field or orthogonal polarization spectral imaging of the sublingual microcirculation, in which the erythrocyte-endothelium gap is estimated, and a tracer dilution technique, in which circulating blood volume is compared with the distribution volume of an ESL-permeable tracer. [30][31][32] Great variability in systemic ESL volume has been reported between different medical conditions, regardless of how ESL volume was estimated. [33][34][35] Mean systemic ESL volume in healthy individuals was shown to be 1.5-1.7 L, whereas much lower systemic ESL volumes were found in treated (1.1 L) and untreated (0.8 L) patients with heterozygous familial hypercholesterolemia and normoalbuminuric (0.8 L) and microalbuminuric (0.2 L) patients with type 1 diabetes.…”

Translational research into vascular wall function: regulatory effects of systemic and specific factors

“…Noninvasive diagnostic methods have been tested to analyze the relationship between the state of endothelial glycocalyx and cardiovascular risk in humans. The analysis employs data obtained with the use of orthogonal polarization spectroscopy (OPS) [12] and sidestream dark field imaging (SDF) [13]. A reverse relationship between the thickness of endothelial glycocalyx in the microcirculatory network and the risk of cardiovascular lesions has been established.…”