Immunoelectrophoretic and immunohistochemical characterizations of fibrinogen derivatives in atherosclerotic aortic intimas and vascular prosthesis pseudo-intimas.
Cadaveric aortic intimas with uncomplicated atherosclerosis were examined to determine the distribution and polypeptide chain composition of fibrinogen-related protein. Immunohistochemical staining showed deposits rich in fibrinopeptides A and B. The deposits were usually disseminated throughout intimas of moderate thickness < 0.7 mm, but were distributed focally in elongate patches bounded both lumenally and medially by deposit-free tissue in thick atheromas. Saline extracts generally showed undegraded monomers and dimers by electrophoresis. The residual protein contained A alpha and gamma-chains that were cross-linked predominantly (>80%) into unresolved high M(r) (>200 kd) derivatives, whereas B beta-chains were left non-cross-linked, as occurs in late stages of cross-linking by transglutaminases. The resolved components had electrophoretic mobilities corresponding to characteristic products of both factor XIIIa and tissue-transglutaminase. A greater incorporation of alpha- rather than gamma-chains into cross-linked products implicated tissue-transglutaminase as contributing heavily. By contrast, vascular graft pseudo-intimas and a cadaveric clot were rich in degraded fibrin devoid of fibrinopeptide A, and cross-linked in patterns typical of XIIIa with gamma 2 dimers constituting the principal product. The findings indicate that the fibrinogen in the aortic intima is comparatively well protected from thrombin and plasmin, and that much of it is deposited through direct cross-linking by tissue-transglutaminase without being converted to fibrin.
Valenzuela
R
R
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio.
Shainoff
J R
JR
DiBello
P M
PM
Urbanic
D A
DA
Anderson
J M
JM
Matsueda
G R
GR
Kudryk
B J
BJ
D000911:Antibodies, Monoclonal; D000941:Antigens; D001011:Aorta / Q000378:metabolism*; D001161:Arteriosclerosis / Q000378:metabolism*; D002102:Cadaver; D005338:Fibrin Fibrinogen Degradation Products; D005340:Fibrinogen / Q000031:analogs & derivatives*; D005345:Fibrinopeptide B / Q000032:analysis; D006801:Humans; D007122:Immunoelectrophoresis; D007150:Immunohistochemistry; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D000941:Antigens; D005338:Fibrin Fibrinogen Degradation Products; C023456:fibrinogen-related antigen; D005345:Fibrinopeptide B; D005340:Fibrinogen