title: Deeper penetration of erythrocytes into the endothelial glycocalyx is associated with impaired microvascular perfusion.
abstract: Changes in endothelial glycocalyx are one of the earliest changes in development of cardiovascular disease. The endothelial glycocalyx is both an important biological modifier of interactions between flowing blood and the vessel wall, and a determinant of organ perfusion. We hypothesize that deeper penetration of erythrocytes into the glycocalyx is associated with reduced microvascular perfusion. The population-based prospective cohort study (the Netherlands Epidemiology of Obesity [NEO] study) includes 6,673 middle-aged individuals (oversampling of overweight and obese individuals). Within this cohort, we have imaged the sublingual microvasculature of 915 participants using sidestream darkfield (SDF) imaging together with a recently developed automated acquisition and analysis approach. Presence of RBC (as a marker of microvascular perfusion) and perfused boundary region (PBR), a marker for endothelial glycocalyx barrier properties for RBC accessibility, were assessed in vessels between 5 and 25 µm RBC column width. A wide range of variability in PBR measurements, with a mean PBR of 2.14 µm (range: 1.43-2.86 µm), was observed. Linear regression analysis showed a marked association between PBR and microvascular perfusion, reflected by RBC filling percentage (regression coefficient β: -0.034; 95% confidence interval: -0.037 to -0.031). We conclude that microvascular beds with a thick ("healthy") glycocalyx (low PBR), reflects efficient perfusion of the microvascular bed. In contrast, a thin ("risk") glycocalyx (high PBR) is associated with a less efficient and defective microvascular perfusion.
authors.affiliation: Department of Nephrology and Einthoven laboratory for Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Dae Hyun
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Nephrology and Einthoven laboratory for Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Martijn J C
authors.initials: MJ
authors.lastname: Dane
authors.affiliation: Department of Nephrology and Einthoven laboratory for Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Bernard M
authors.initials: BM
authors.lastname: van den Berg
authors.affiliation: Department of Nephrology and Einthoven laboratory for Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Margien G S
authors.initials: MG
authors.lastname: Boels
authors.affiliation: Department of Physiology and Glycocheck, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Jurgen W
authors.initials: JW
authors.lastname: van Teeffelen
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Renée
authors.initials: R
authors.lastname: de Mutsert
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.affiliation: Department of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Johan
authors.initials: J
authors.lastname: van der Vlag
authors.affiliation: Department of Nephrology and Einthoven laboratory for Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Anton Jan
authors.initials: AJ
authors.lastname: van Zonneveld
authors.affiliation: Department of Physiology and Glycocheck, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: Vink
authors.affiliation: Department of Nephrology and Einthoven laboratory for Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
mesh_terms: D015992:Body Mass Index; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology; D003430:Cross-Sectional Studies; D003952:Diagnostic Imaging / Q000379:methods; D004730:Endothelium, Vascular / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D019276:Glycocalyx / Q000378:metabolism*; D006801:Humans; D016014:Linear Models; D008297:Male; D055806:Microvessels / Q000378:metabolism*; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009765:Obesity / Q000175:diagnosis / Q000453:epidemiology; D010477:Perfusion; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D011795:Surveys and Questionnaires