Document Detail


Partial recovery of the endothelial glycocalyx upon rosuvastatin therapy in patients with heterozygous familial hypercholesterolemia.
MedLine Citation:
PMID:  18695266     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Marijn C Meuwese; Hans L Mooij; Max Nieuwdorp; Bart van Lith; Roos Marck; Hans Vink; John J P Kastelein; Erik S G Stroes
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-08-11
Journal Detail:
Title:  Journal of lipid research     Volume:  50     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2009 Jan 
Date Detail:
Created Date:  2008-12-16     Completed Date:  2009-04-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  148-53     Citation Subset:  IM    
Affiliation:
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adult
Anticholesteremic Agents / pharmacology
Atherosclerosis / genetics,  metabolism
Cardiovascular Diseases / genetics
Cholesterol, LDL / metabolism
Dextrans / metabolism
Endothelium / metabolism
Fluorobenzenes / therapeutic use*
Glycocalyx / drug effects*,  metabolism*
Heterozygote*
Humans
Hypercholesterolemia / genetics*
Male
Middle Aged
Permeability
Pyrimidines / therapeutic use*
Sulfonamides / therapeutic use*
Chemical
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Cholesterol, LDL; 0/Fluorobenzenes; 0/Pyrimidines; 0/Sulfonamides; 287714-41-4/rosuvastatin; 9004-54-0/Dextrans

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