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.
Highlights
Cardiovascular disease is the leading cause of death in developed countries and one of the earliest changes in the pathogenesis of cardiovascular disease is microvascular dysfunction [1]
Association of the glycocalyx barrier properties with microcirculatory perfusion To test the hypothesis whether impaired glycocalyx barrier properties are associated with impaired microvascular perfusion, we examined the association between perfused boundary region (PBR) and the two used estimates for microvascular perfusion (Table 3 and figure 2)
We have measured the red blood cells (RBC) accessibility into the endothelial glycocalyx, i.e. perfused boundary region (PBR) together with RBC filling percentage and valid microvascular density in the sublingual microvasculature of over 900 participants recruited for the Netherlands Epidemiology of Obesity (NEO) study
Summary
Cardiovascular disease is the leading cause of death in developed countries and one of the earliest changes in the pathogenesis of cardiovascular disease is microvascular dysfunction [1]. Within the inner vessel wall, a luminal endothelial glycocalyx is strategically located to continuously interact with the flowing blood. This endothelial glycocalyx is a thick gel-like meshwork of proteoglycans, glycosaminoglycans and plasma proteins; it functions as an important biological modifier in the interaction between the blood and the vessel wall [2,3]. Degradation and modification of the endothelial glycocalyx is, thought to be one of the earliest changes occurring in the pathogenesis of vascular disease [4,5]. The endothelial glycocalyx has a protective role against protein leakage, as shown by our group previously, when selective degradation of endothelial glycocalyx with hyaluronidase led to glomerular albumin leakage [4]
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