Abstract
There is increasing recognition of the importance of the endothelial glycocalyx and
its in vivo manifestation, the endothelial surface layer, in vascular homeostasis.
Heparan sulfate proteoglycans (HSPGs) are a major structural constituent of the endothelial
glycocalyx and serve to regulate vascular permeability, microcirculatory tone, leukocyte
and platelet adhesion, and hemostasis. During sepsis, endothelial HSPGs are shed through
the induction of “sheddases” such as heparanase and matrix metalloproteinases, leading
to loss of glycocalyx integrity and consequent vascular dysfunction. Less well recognized
is that glycocalyx degradation releases HSPG fragments into the circulation, which
can shape the systemic consequences of sepsis. In this review, we will discuss (1)
the normal, homeostatic functions of HSPGs within the endothelial glycocalyx, (2)
the pathological changes in HSPGs during sepsis and their consequences on the local
vascular bed, and (3) the systemic consequences of HSPG degradation. In doing so,
we will identify potential therapeutic targets to improve vascular function during
sepsis as well as highlight key areas of uncertainty that require further mechanistic
investigation.
Keywords
endothelial glycocalyx - sepsis - heparan sulfate proteoglycans
