Vascular repair utilising immobilised heparin conjugate for protection against early activation of inflammation and coagulation

Thrombosis and Haemostasis
Sofia NordlingPeetra U Magnusson

Abstract

Ischaemia-reperfusion injury (IRI) poses a major challenge in many thrombotic conditions and in whole organ transplantation. Activation of the endothelial cells and shedding of the protective vascular glycocalyx during IRI increase the risk of innate immune activation, cell infiltration and severe thrombus formation, promoting damage to the tissue. Here, we present a novel one-step strategy to protect the vasculature by immobilisation of a unique multi-arm heparin conjugate to the endothelium. Applying a new in vitro blood endothelial cell chamber model, the heparin conjugate was found to bind not only to primary human endothelial cells but also directly to the collagen to which the cells adhered. Incubation of hypoxic endothelial cells with freshly drawn human blood in the blood chambers elicited coagulation activation reflected by thrombin anti-thrombin formation and binding of platelets and neutrophils. Immobilisation of the heparin conjugate to the hypoxic endothelial cells created a protective coating, leading to a significant reduction of the recruitment of blood cells and coagulation activation compared to untreated hypoxic endothelial cells. This novel approach of immobilising multi-arm heparin conjugates on the endothe...Continue Reading

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Citations

Dec 23, 2015·Thrombosis and Haemostasis·Christian Weber, Gregory Y H Lip
Sep 13, 2016·Journal of Intensive Care·Akira UshiyamaTakehiko Iijima
Jul 14, 2016·Clinical and Experimental Nephrology·Raimo TuuminenRiitta Lassila
Mar 5, 2019·Chinese Medical Journal·Rui-Na CaoRui Xia
Apr 9, 2019·Chinese Medical Journal·Rui-Na CaoRui Xia
May 28, 2020·Frontiers in Physiology·Laura KummerJan Larmann
May 3, 2018·Critical Care : the Official Journal of the Critical Care Forum·Andreas MargrafJan Rossaint
Jan 16, 2019·BioMed Research International·C SteichenR Thuillier
Mar 27, 2020·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Antonio MuscariMarco Zoli
Dec 15, 2020·International Immunopharmacology·Brina StančičPeetra U Magnusson

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