Deeper penetration of erythrocytes into the endothelial glycocalyx is associated with impaired microvascular perfusion

PLoS One. 2014 May 9;9(5):e96477. doi: 10.1371/journal.pone.0096477. eCollection 2014.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Body Mass Index
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / epidemiology
  • Cross-Sectional Studies
  • Diagnostic Imaging / methods
  • Endothelium, Vascular / metabolism*
  • Erythrocytes / metabolism*
  • Female
  • Glycocalyx / metabolism*
  • Humans
  • Linear Models
  • Male
  • Microvessels / metabolism*
  • Middle Aged
  • Netherlands / epidemiology
  • Obesity / diagnosis
  • Obesity / epidemiology
  • Perfusion
  • Population Surveillance / methods
  • Prospective Studies
  • Surveys and Questionnaires

Grant support

This work was supported by the Dutch Kidney Foundation [grant number C08.2265 and CP09.03]. The NEO study is supported by participating departments, the Division and the Board of Directors of the Leiden University Medical Center, and by the Leiden University, Research Profile Area ‘Vascular and Regenerative Medicine’. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.