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

Marijn C Meuwese,Hans L Mooij,Max Nieuwdorp,Bart Van Lith,Roos Marck,Hans Vink,John J.P Kastelein,Erik S.G Stroes

doi:10.1194/jlr.p800025-jlr200

Marijn C Meuwese, Hans L Mooij + Show 6 more

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https://doi.org/10.1194/jlr.p800025-jlr200

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Abstract

The endothelial glycocalyx has been shown to serve as a protective barrier between the flowing blood and the vessel wall in experimental models. The aim of this study was to evaluate whether hypercholesterolemia is associated with glycocalyx perturbation in humans, and if so, whether statin treatment can restore this. We measured systemic glycocalyx volume (V(G)) in 13 patients with heterozygous familial hypercholesterolemia (FH) after cessation of lipid-lowering therapy for a minimum of 4 weeks and 8 weeks after initiating rosuvastatin therapy. Normocholesterolemic subjects were used as controls. V(G) was estimated by subtracting the intravascular distribution volume of a glycocalyx permeable tracer (dextran 40) from that of a glycocalyx impermeable tracer (labeled erythrocytes). V(G) in untreated FH patients [LDL 225 +/- 57 mg/dl (mean +/- SD)] was significantly reduced compared with controls (LDL 93 +/- 24 mg/dl) (V(G) 0.8 +/- 0.3 vs. 1.7 +/- 0.6, respectively, P < 0.001). After normalization of LDL levels (95 +/- 33 mg/dl) upon 8 weeks of statin treatment, V(G) recovered only partially (V(G) 1.1 +/- 0.4 L, P = 0.04). The endothelial glycocalyx is profoundly reduced in FH patients, which may contribute to increased atherogenic vulnerability. This perturbation is partially restored upon short-term statin therapy.

Highlights

The endothelial glycocalyx has been shown to serve as a protective barrier between the flowing blood and the vessel wall in experimental models
In the present study we evaluated whether hypercholesterolemia is associated with glycocalyx perturbation in Abbreviations: CRP, C-reactive protein; FH, familial hypercholesterolemia; Ht, hematocrit; orthogonal polarization spectral (OPS), orthogonal polarization spectroscopy; oxLDL, oxidized low-density lipoproteins; VG, systemic glycocalyx volume
HDL-cholesterol levels, triglyceride levels, blood pressure, as well as CRP were all within the normal range, but significantly less favorable in FH patients compared with controls

Summary

Introduction

The endothelial glycocalyx has been shown to serve as a protective barrier between the flowing blood and the vessel wall in experimental models. The endothelial glycocalyx is profoundly reduced in FH patients, which may contribute to increased atherogenic vulnerability This perturbation is partially restored upon short-term statin therapy.—Meuwese, M. Gorog and Born [4] already found that sialic acid density in rabbits was decreased in predilection sites for atherosclerosis These findings have been corroborated, because loss of glycocalyx leads to a wide spectrum of vascular abnormalities in experimental models. Our group developed a novel technique to estimate the volume of the endothelial glycocalyx in humans Using this method, Nieuwdorp et al [9] showed that acute hyperglycemia results in a profound perturbation of the glycocalyx, coinciding with vascular dysfunction and activation of the coagulation system. Other risk factors such as oxygen radical stress, inflammation, and exposure to oxidized low-density lipoprotein (oxLDL) have been shown to disrupt the glycocalyx [8, 12,13,14]

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