New functional tools for anti-thrombogenic activity assessment of live surface glycocalyx
Loading...
Authors
Dimitrievska, S.
Weyers, A.
Lin, T.
Cai, C.
Wu, W.
Tuggle, C.T.
Sundaram, S.
Balestrini, J.L.
Slattery, D.
Tchouta, L.
Issue Date
2016
Type
Article
Language
ENG
Keywords
Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
Alternative Title
Abstract
Objective: It is widely accepted that the presence of a glycosaminoglycan-rich glycocalyx is essential for endothelialized vasculature health; in fact, a damaged or impaired glycocalyx has been demonstrated in many vascular diseases. Currently, there are no methods that characterize glycocalyx functionality, thus limiting investigators' ability to assess the role of the glycocalyx in vascular health. Approach and results: We have developed novel, easy-to-use, in vitro assays that directly quantify live endothelialized surface's functional heparin weights and their anticoagulant capacity to inactivate Factor Xa and thrombin. Using our assays, we characterized 2 commonly used vascular models: native rat aorta and cultured human umbilical vein endothelial cell monolayer. We determined heparin contents to be ≈10 000 ng/cm(2) on the native aorta and ≈10-fold lower on cultured human umbilical vein endothelial cells. Interestingly, human umbilical vein endothelial cells demonstrated a 5-fold lower anticoagulation capacity in inactivating both Factor Xa and thrombin relative to native aortas. We verified the validity and accuracy of the novel assays developed in this work using liquid chromatography-mass spectrometry analysis. Conclusions: Our assays are of high relevance in the vascular community because they can be used to establish the antithrombogenic capacity of many different types of surfaces such as vascular grafts and transplants. This work will also advance the capacity for glycocalyx-targeting therapeutics development to treat damaged vasculatures.
Description
Arteriosclerosis, Thrombosis, and Vascular Biology, 36, 1847-1853
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Note : if this item contains full text it may be a preprint, author manuscript, or a Gold OA copy that permits redistribution with a license such as CC BY. The final version is available through the publisher’s platform.
Full Citation
New functional tools for anti-thrombogenic activity assessment of live surface glycocalyx, S. Dimitrievska, A. Weyers, T. Lin, C. Cai, W. Wu, C. T. Tuggle, S. Sundaram, J. L. Balestrini, D. Slattery, L. Tchouta, T. R. Kyriakides, J. M. Tarbell, R.J. Linhardt, L. E. Niklason, Arteriosclerosis, Thrombosis, and Vascular Biology, 36, 1847-1853, 2016.
Publisher
American Heart Association (AHA) Journals and Wiley