- Review
- Open Access
- Published:
The glycocalyx: a novel diagnostic and therapeutic target in sepsis
Abstract
The
glycocalyx is a gel-like layer covering the luminal surface of vascular
endothelial cells. It is comprised of membrane-attached proteoglycans,
glycosaminoglycan chains, glycoproteins, and adherent plasma proteins.
The glycocalyx maintains homeostasis of the vasculature, including
controlling vascular permeability and microvascular tone, preventing
microvascular thrombosis, and regulating leukocyte adhesion.
During sepsis, the glycocalyx is degraded via inflammatory mechanisms such as
metalloproteinases (MMP genes : Zinc dependent endopeptidases, https://www.ncbi.nlm.nih.gov/pubmed/28413025 )
heparanase (HPSE genes, https://www.ncbi.nlm.nih.gov/gene; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447241/ ;
and hyaluronidase.(HYAL genes 1-5, https://www.ncbi.nlm.nih.gov/gene )
These sheddases ( ACE2 is Zn- metalloprotein and ADAM17 is a sheddase, https://www.ncbi.nlm.nih.gov/gene/6868 A Disintegrin And Metalloproteinase 17: https://www.ncbi.nlm.nih.gov/pubmed/31564162 Thalamic pain treshold?)
are activated by reactive oxygen species (ROS) and pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL1-beta).
Inflammation-mediated glycocalyx degradation leads to vascular hyper-permeability, unregulated vasodilation, microvessel thrombosis, and augmented leukocyte adhesion.
Clinical studies have demonstrated the correlation between blood levels of glycocalyx components with organ dysfunction, severity, and mortality in sepsis.
Fluid resuscitation therapy is an essential part of sepsis treatment, but overaggressive fluid therapy practices (leading to hypervolemia) may augment glycocalyx degradation.
Conversely, fresh frozen plasma and albumin administration may attenuate glycocalyx degradation. The beneficial and harmful effects of fluid and plasma infusion on glycocalyx integrity in sepsis are not well understood; future studies are warranted.
In this review, we first analyze the underlying mechanisms of glycocalyx degradation in sepsis. Second, we demonstrate how the blood and urine levels of glycocalyx components are associated with patient outcomes. Third, we show beneficial and harmful effects of fluid therapy on the glycocalyx status during sepsis. Finally, we address the concept of glycocalyx degradation as a therapeutic target.
...
During sepsis, the glycocalyx is degraded via inflammatory mechanisms such as
metalloproteinases (MMP genes : Zinc dependent endopeptidases, https://www.ncbi.nlm.nih.gov/pubmed/28413025 )
heparanase (HPSE genes, https://www.ncbi.nlm.nih.gov/gene; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5447241/ ;
and hyaluronidase.(HYAL genes 1-5, https://www.ncbi.nlm.nih.gov/gene )
These sheddases ( ACE2 is Zn- metalloprotein and ADAM17 is a sheddase, https://www.ncbi.nlm.nih.gov/gene/6868 A Disintegrin And Metalloproteinase 17: https://www.ncbi.nlm.nih.gov/pubmed/31564162 Thalamic pain treshold?)
are activated by reactive oxygen species (ROS) and pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL1-beta).
Inflammation-mediated glycocalyx degradation leads to vascular hyper-permeability, unregulated vasodilation, microvessel thrombosis, and augmented leukocyte adhesion.
Clinical studies have demonstrated the correlation between blood levels of glycocalyx components with organ dysfunction, severity, and mortality in sepsis.
Fluid resuscitation therapy is an essential part of sepsis treatment, but overaggressive fluid therapy practices (leading to hypervolemia) may augment glycocalyx degradation.
Conversely, fresh frozen plasma and albumin administration may attenuate glycocalyx degradation. The beneficial and harmful effects of fluid and plasma infusion on glycocalyx integrity in sepsis are not well understood; future studies are warranted.
In this review, we first analyze the underlying mechanisms of glycocalyx degradation in sepsis. Second, we demonstrate how the blood and urine levels of glycocalyx components are associated with patient outcomes. Third, we show beneficial and harmful effects of fluid therapy on the glycocalyx status during sepsis. Finally, we address the concept of glycocalyx degradation as a therapeutic target.
...
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