Summary
Vitronectin (VN) stabilizes plasminogen activator inhibitor type 1 (PAI-1) activity
and prevents the fibrin(ogen)-induced acceleration of plasminogen activation by t-PA.
These antifibrinolytic activities as well as other functions are mediated by the glycosaminoglycan
(GAG) binding domain of VN. Since the GAG binding region is rich in arginyl and lysyl
residues, it is a potential target for enzymes such as plasmin. In this paper, the
dose and time-dependent proteolysis of VN by plasmin is demonstrated. The addition
of urokinase or streptokinase (200 units/ml) to plasma also produced proteolysis of
VN. With minimal proteolysis, the 75 kDa band was degraded to a 62-65 kDa form of
VN. This minimal proteolysis destroyed the binding of [3H]-heparin to VN and reversed the neutralization of heparin by VN.
Thus, the plasmin-mediated proteolysis of the GAG binding activity of VN could destroy
the antifibrinolytic activity of VN during physiologic conditions and during thrombolytic
therapy. Furthermore, other functions of VN in complement and coagulation systems
that are mediated by the GAG binding domain may be destroyed by plasmin proteolysis.
