Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6002248 | Thrombosis Research | 2014 | 8 Pages |
Abstract
MGO concentration-dependently attenuated inhibition of thrombin and factor Xa by ATIII in PBS-based assays, both in the presence and absence of heparin. In addition, MGO concentration-dependently inhibited ATIII activity in a plasma-based system, to the level of plasma completely deficient in ATIII, again both in the presence and absence of heparin. Results from LC-MS/MS experiments revealed that MGO covalently adducts the active site Arg 393 of ATIII through two distinct glyoxalation mechanisms. We posit that active site adduction is the mechanism of MGO-mediated inhibition of ATIII, and thus contributes to the underlying pathophysiology of the diabetic hypercoagulable state and complications thereof.
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Authors
Richard Jacobson, Nicholas Mignemi, Kristie Rose, Lynda O'Rear, Suryakala Sarilla, Heidi E. Hamm, Joey V. Barnett, Ingrid M. Verhamme, Jonathan Schoenecker,