title: Damage of the endothelial glycocalyx in chronic kidney disease.
abstract: OBJECTIVE
  The endothelial glycocalyx (eGC), a mesh of anionic biopolymers covering the luminal surface of endothelial cells, is considered as an intravascular compartment that protects the vessel wall against pathogenic insults in cardiovascular disease. We hypothesized that chronic kidney disease (CKD) is associated with reduced eGC integrity and subsequent endothelial dysfunction.
  
  
  RESULTS
  Shedding of two major components of the eGC, namely syndecan-1 (Syn-1) and hyaluronan (HA), was measured by ELISA in 95 patients with CKD (stages 3-5) and 31 apparently healthy controls. Plasma levels of Syn-1 and HA increased steadily across CKD stages (5- and 5.5-fold, respectively P < 0.001) and were independently associated with impaired renal function after multivariate adjustment. Furthermore, Syn-1 and HA correlated tightly with plasma markers of endothelial dysfunction such as soluble fms-like tyrosine kinase-1 (sFlt-1), soluble vascular adhesion molecule-1 (sVCAM-1), von-Willebrand-Factor (vWF) and angiopoietin-2 (P < 0.001). Experimentally, excessive shedding of the eGC, evidenced by 11-fold increased Syn-1 plasma levels, was also observed in an established rat model of CKD, the 5/6-nephrectomized rats. Consistently, an atomic force microscopy-based approach evidenced a significant decrease in eGC thickness (360 ± 79 vs. 157 ± 29 nm, P = 0.001) and stiffness (0.33 ± 0.02 vs. 0.22 ± 0.01 pN/nm, P < 0.001) of aorta endothelial cell explants isolated from CKD rats.
  
  
  CONCLUSIONS
  Our findings provide evidence for damage of the atheroprotective eGC as a consequence of CKD and potentially open a new avenue to pathophysiology and treatment of cardiovascular disease in renal patients.
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1 A1, 48149 Münster, Germany.
authors.forename: Jan-Sören
authors.initials: JS
authors.lastname: Padberg
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1 A1, 48149 Münster, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Wiesinger
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1 A1, 48149 Münster, Germany.
authors.forename: Giovana Seno
authors.initials: GS
authors.lastname: di Marco
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1 A1, 48149 Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Reuter
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1 A1, 48149 Münster, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Grabner
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1 A1, 48149 Münster, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Kentrup
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1 A1, 48149 Münster, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Lukasz
authors.affiliation: Institute of Physiology II, University of Muenster, Robert-Koch-Straße 27 b, 48149 Münster, Germany.
authors.forename: Hans
authors.initials: H
authors.lastname: Oberleithner
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1 A1, 48149 Münster, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstädt
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1 A1, 48149 Münster, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Brand
authors.affiliation: Department of Medicine D, Division of General Internal Medicine, Nephrology, and Rheumatology, University Hospital Münster, Albert-Schweitzer-Campus 1 A1, 48149 Münster, Germany. Electronic address: philipp.kuempers@ukmuenster.de.
authors.forename: Philipp
authors.initials: P
authors.lastname: Kümpers
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D018450:Disease Progression; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology*; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D019276:Glycocalyx / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D007668:Kidney / Q000503:physiopathology; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D053668:Syndecan-1 / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015415:Biomarkers; C508241:SDC1 protein, human; C508243:Sdc1 protein, rat; D053668:Syndecan-1; D006820:Hyaluronic Acid
keywords: 5/6 Nephrectomy; Atherosclerosis; Atomic force microscopy; Cardiovascular disease; Chronic kidney disease; Endothelial glycocalyx; Hyaluronan; Shedding; Syndecan-1