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Title A positively charged surface triggers coagulation activation through factor VII activating protease (FSAP)
Date 14.11.2017
Number 53989
Abstract Contact between biomedical materials and blood often initiates undesirable pro-coagulant and pro-inflammatory processes. On negatively charged materials, blood coagulation is known to be triggered through autoactivation of Factor XII, while activation on cationic surfaces follows a distinct and so far enigmatic mechanism. Because Factor VII activating protease (FSAP) is known to be activated on positively and on negatively charged macromolecules in plasma, we have investigated its interaction with charged biomaterials and its consequences for coagulation. Several activation processes in blood and plasma were characterized after contact with material surfaces with varied charge. FSAP was found to be exclusively activated by the positively charged surfaces polyethylenimine (PEI) and poly-l-lysine (PLL), not by the negatively charged glass or self-assembled monolayer with carboxyl group termination (SAM-COOH), as well as uncharged (Teflon AF) surfaces. Whole blood incubation on PEI showed that this activation was concomitant with coagulation as determined by thrombin and fibrin formation, which was high for glass (F1+2, 138 nM) and PEI (F1+2, 44 nM) but low for Teflon AF (F1+2, 3.3 nM) and SAM COOH (F1+2, 5.8 nM). Contact phase inhibitor diminished coagulation to background levels for all surfaces except PEI (F1+2: ^PEI 43 to 25 nM; glass, 58 to 1.5 nM) indicating that coagulation activation is not dependent on FXII activation on the PEI surface. A decisive role of endogenous FSAP for coagulation however was confirmed with the use of FSAP inhibitory antibodies which showed no influence on Teflon AF, glass and SAM COOH but diminished F1+2 on PEI to less than 50%. We propose that FSAP activation could be a novel mechanism of surface-driven coagulation. An inhibition of this protease might improve hemocompatibility of cationic surfaces and therefore facilitate the application of polycationic surfaces in blood.
URL http://dx.doi.org/10.1021/acsami.7b14281
Publisher ACS Applied Materials & Interfaces
Identifier 0
Citation ACS Applied Materials & Interfaces 9 (2017) 40107-40116
DOI http://dx.doi.org/10.1021/acsami.7b14281
Authors Sperling, C. ; Maitz, M.F. ; Grasso, S. ; Werner, C. ; Kanse, S. M.
Tags blood coagulation cascade charged biomaterials factor seven activating protease habp2 hemocompatibility polyethylenimine hyaluronan-binding protein factor pathway inhibitor tissue factor expression blood factor-xii contact activation platelet-adhesion in-

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