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Journal of Lipid Research, Vol. 50, 148-153, January 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

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^* and Erik S. G. Stroes^1,*

^* Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands
Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands

Published, JLR Papers in Press, August 11, 2008.

This study was funded by a research grant from the Netherlands Heart Foundation to E.S.G. Stroes (2006B088). H. Vink is an established investigator of The Netherlands Heart Foundation (2005T037). J.J.P. Kastelein is a clinical established investigator of the Netherlands Heart Foundation (2000D039). Astra Zeneca provided funding for rosuvastatin.

¹ To whom correspondence should be addressed. e-mail: e.s.stroes{at}amc.uva.nl

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.

Supplementary key words glycosaminoglycans • LDL cholesterol • atherosclerosis

Abbreviations: CRP, C-reactive protein; FH, familial hypercholesterolemia; Ht, hematocrit; OPS, orthogonal polarization spectroscopy; oxLDL, oxidized low-density lipoproteins; V_G, systemic glycocalyx volume

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