Cystamine preparations exhibit anticoagulant activity.
Transglutaminases are a superfamily of isoenzymes found in cells and plasma. These enzymes catalyze the formation of ε-N-(γ-glutamyl)-lysyl crosslinks between proteins. Cystamine blocks transglutaminase activity and is used in vitro in human samples and in vivo in mice and rats in studies of coagulation, immune dysfunction, and inflammatory disease. These studies have suggested cystamine blocks fibrin crosslinking and has anti-inflammatory effects, implicating transglutaminase activity in the pathogenesis of several diseases. We measured the effects of cystamine on fibrin crosslinking, tissue factor-triggered plasma clot formation and thrombin generation, and coagulation factor enzymatic activity. At concentrations that blocked fibrin crosslinking, cystamine also inhibited plasma clot formation and reduced thrombin generation. Cystamine inhibited the amidolytic activity of coagulation factor XI and thrombin towards chromogenic substrates. These findings demonstrate that cystamine exhibits anticoagulant activity during coagulation. Given the close relationship between coagulation and inflammation, these findings suggest prior studies that used cystamine to implicate transglutaminase activity in disease pathogenesis warrant re-examination.
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Maria M
MM
Aleman
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Lori A
LA
Holle
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Katherine G
KG
Stember
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Christa I
CI
Devette
McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Dougald M
DM
Monroe
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America; McAllister Heart Institute, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America.
Alisa S
AS
Wolberg
D000818:Animals; D000925:Anticoagulants / Q000737:chemistry* / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D003538:Cystamine / Q000737:chemistry* / Q000494:pharmacology*; D015945:Factor XIa / Q000378:metabolism; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D051379:Mice; D051381:Rats; D013917:Thrombin; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000378:metabolism
D000925:Anticoagulants; D005337:Fibrin; D011503:Transglutaminases; D015945:Factor XIa; D013917:Thrombin; D003538:Cystamine