Partial recovery of the endothelial glycocalyx upon rosuvastatin therapy in patients with heterozygous familial hypercholesterolemia.
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.
Meuwese
Marijn C
MC
Department of Vascular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
Mooij
Hans L
HL
Nieuwdorp
Max
M
van Lith
Bart
B
Marck
Roos
R
Vink
Hans
H
Kastelein
John J P
JJ
Stroes
Erik S G
ES
D000328:Adult; D000924:Anticholesteremic Agents / Q000494:pharmacology; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000235:genetics; D008078:Cholesterol, LDL / Q000378:metabolism; D003911:Dextrans / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism; D005464:Fluorobenzenes / Q000627:therapeutic use*; D019276:Glycocalyx / Q000187:drug effects* / Q000378:metabolism*; D006579:Heterozygote; D006801:Humans; D006937:Hypercholesterolemia / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010539:Permeability; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000627:therapeutic use*
D000924:Anticholesteremic Agents; D008078:Cholesterol, LDL; D003911:Dextrans; D005464:Fluorobenzenes; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium