Targeting hyaluronan of the endothelial glycocalyx for therapeutic intervention.
The endothelial glycocalyx (EG) is an extracellular matrix (ECM) coating the luminal surface of the vascular endothelium. Hyaluronan (HA), a glycosaminoglycan, is an important constituent of the EG that regulates inflammation and repair. By providing a direct link between the endothelium and its ECM, HA contributes to maintaining glycocalyx integrity; emerging evidence indicates a close association between EG deterioration, concomitant loss of HA and the onset of endothelial dysfunction, a phenomenon that is involved in many disorders, including atherosclerosis, diabetes, hypertension and dyslipidemia. This review provides an overview of glycocalyx modification by pathological stimuli and considers the potential of the pharmacological targeting of HA synthesis and binding to limit endothelial dysfunction and to improve vasculoprotection.
Wheeler-Jones
Caroline P D
CP
Royal Veterinary College, Department of Veterinary Basic Sciences, Royal College Street, London, NW1 0TU, UK. cwheeler@rvc.ac.uk
Farrar
Charlotte E
CE
Pitsillides
Andrew A
AA
D000818:Animals; D050197:Atherosclerosis / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019276:Glycocalyx / Q000187:drug effects* / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000096:biosynthesis / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism; D058990:Molecular Targeted Therapy
D006025:Glycosaminoglycans; D018960:Hyaluronan Receptors; D006820:Hyaluronic Acid