Fibrinogen A alpha and gamma-chain dimers as potential differential indicators of atherosclerotic and thrombotic vascular disease.
Cross-linked fibrin(ogen) dimers are known to be elevated in the plasma of subjects with occlusive vascular disease, and are thought to be fibrin dimers. Immunoelectrophoretic analyses of the dimers, however, indicate that (1) they are predominantly fibrinogen rather than fibrin dimers, and (2) they contain cross-linked A alpha-chains (A alpha-dyads) instead of the gamma-chain dyads that are rapidly formed by factor XIII during blood coagulation. Furthermore, the mobilities of the A alpha-dyads differ from the cross-linked alpha-chain products that accompany the gamma-chain cross-linking by factor XIII. Instead, the mobilities coincide with the distinct A alpha-dyads that are produced by tissue transglutaminase, an intracellular enzyme not normally present in plasma. The intimal fibrinogen deposits in atherosclerotic aortas also possess fibrinopeptide A and cross-linked A alpha-chains. Thus, both the plasma fibrinogen dimers and the intimal fibrinogen deposits appear to derive from the action of released tissue transglutaminase more so than factor XIII. It is proposed that, in the absence of other indications of cytolytic processes, the levels of A alpha-dyads in plasma reflect ongoing cellular injury accompanying atherogenesis. The extent to which gamma-dyads accompany the A alpha-dyads may signal progression of the disease to advanced stages in which ulcerations and occlusive lesions trigger thrombotic complications.
Shainoff
J R
JR
Research Institute, Cleveland Clinic Foundation, OH 44195.
Valenzuela
R
R
Urbanic
D A
DA
DiBello
P M
PM
Lucas
F V
FV
Graor
R
R
D001161:Arteriosclerosis / Q000378:metabolism*; D015415:Biomarkers; D004587:Electrophoresis, Agar Gel / Q000379:methods; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D005340:Fibrinogen / Q000032:analysis*; D006801:Humans; D007122:Immunoelectrophoresis / Q000379:methods; D013924:Thrombophlebitis / Q000097:blood; D013927:Thrombosis / Q000378:metabolism*; D011503:Transglutaminases / Q000378:metabolism
D015415:Biomarkers; C027539:fibrinopeptides gamma; D005340:Fibrinogen; D011503:Transglutaminases