Abstract
Expressed on the endothelial cell (EC) surface of blood vessels, the glycocalyx (GCX), a mixture of carbohydrates attached to proteins, regulates the access of cells and molecules in the blood to the endothelium. Besides protecting endothelial barrier integrity, the dynamic microstructure of the GCX confers remarkable functions including mechanotransduction and control of vascular tone. Recently, a novel perspective has emerged supporting the pleiotropic roles of the endothelial GCX (eGCX) in cardiovascular health and disease. Because eGCX degradation occurs in certain pathological states, the circulating levels of eGCX degradation products have been recognized to have diagnostic or prognostic values. Beyond their biomarker roles, certain eGCX fragments serve as pathogenic factors in disease progression. Pharmacological interventions that attenuate eGCX degradation or restore its integrity have been sought. This review provides our current understanding of eGCX structure and function across the microvasculature in different organs. We also discuss disease or injury states, such as infection, sepsis and trauma, where eGCX dysfunction contributes to severe inflammatory vasculopathy.
Highlights
The vascular endothelial surface is coated by the GCX matrix that confers important functions in circulatory homeostasis (Weinbaum et al, 2007)
Unlike other endothelial GCX (eGCX) constituents, hyaluronic acid is a linear, non-sulfated GAG that interacts with the cell surface receptor CD44, a glycoprotein (Aruffo et al, 1990)
Disruption of eGCX is a consequence as well as cause of microvascular injury, as eGCX degradation products act as pathogenic factors capable of inducing endothelial hyperpermeability and microvascular leakage during inflammation
Summary
The vascular endothelial surface is coated by the GCX matrix that confers important functions in circulatory homeostasis (Weinbaum et al, 2007). The eGCX modulates vascular permeability and hydraulic conductivity by limiting the flux of water and macromolecules (Curry and Michel, 1980; Adamson, 1990; Curry, 2005; Lennon and Singleton, 2011; Curry and Adamson, 2012) It acts as a vascular barrier through modulation of molecular binding to the EC surface due to the high density of anionic charges on its GAGs side chains. In organs like the brain and heart, where the capillary endothelium is categorized as continuous (non-fenestrated), the endothelial eGCX appears to be denser compared to that in the lung, whose capillaries are covered by continuous endothelium (Ando et al, 2018) These differences might be explained by the mechanotransduction properties of the eGCX in sensing fluid shear stress, which alters GAGs synthesis (Arisaka et al, 1995; Gouverneur et al, 2006; Zeng and Tarbell, 2014). Gene expression profiling and single–cell RNA-sequencing might yield a more comprehensive picture of the distinct EC subsets and associated eGCX structures (Jambusaria et al, 2020; Gao and Galis, 2021)
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