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Pharmaceuticals 2017, 10(2), 36; doi:10.3390/ph10020036

Development of a Glycosaminoglycan Derived, Selectin Targeting Anti-Adhesive Coating to Treat Endothelial Cell Dysfunction

1
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN 47907, USA
2
Indiana University School of Medicine, Indianapolis, IN 46202, USA
3
Department of Biomedical Engineering, University of California—Davis, Davis, CA 95616, USA
*
Author to whom correspondence should be addressed.
Academic Editor: Barbara Mulloy
Received: 24 January 2017 / Revised: 22 March 2017 / Accepted: 24 March 2017 / Published: 29 March 2017
(This article belongs to the Special Issue Glycosaminoglycans and Proteoglycans)
View Full-Text   |   Download PDF [4859 KB, uploaded 29 March 2017]   |  

Abstract

Endothelial cell (EC) dysfunction is associated with many disease states including deep vein thrombosis (DVT), chronic kidney disease, sepsis and diabetes. Loss of the glycocalyx, a thin glycosaminoglycan (GAG)-rich layer on the EC surface, is a key feature of endothelial dysfunction and increases exposure of EC adhesion molecules such as selectins, which are involved in platelet binding to ECs. Once bound, platelets cause thrombus formation and an increased inflammatory response. We have developed a GAG derived, selectin targeting anti-adhesive coating (termed EC-SEAL) consisting of a dermatan sulfate backbone and multiple selectin-binding peptides designed to bind to inflamed endothelium and prevent platelet binding to create a more quiescent endothelial state. Multiple EC-SEAL variants were evaluated and the lead variant was found to preferentially bind to selectin-expressing ECs and smooth muscle cells (SMCs) and inhibit platelet binding and activation in a dose-dependent manner. In an in vivo model of DVT, treatment with the lead variant resulted in reduced thrombus formation. These results indicate that EC-SEAL has promise as a potential therapeutic in the treatment of endothelial dysfunction. View Full-Text
Keywords: glycocalyx; endothelial cell; dysfunction; selectin; dermatan sulfate; deep vein thrombosis glycocalyx; endothelial cell; dysfunction; selectin; dermatan sulfate; deep vein thrombosis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Wodicka, J.R.; Chambers, A.M.; Sangha, G.S.; Goergen, C.J.; Panitch, A. Development of a Glycosaminoglycan Derived, Selectin Targeting Anti-Adhesive Coating to Treat Endothelial Cell Dysfunction. Pharmaceuticals 2017, 10, 36.

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