The Role of The Plasminogen-Fibrin Interaction in The Regulation of Fibrinolysis

Fibrinolysis refers to the proteolytic mechanism whereby the body dissoloves intravascular deposits of fibrin, a process important in maintaining the patency of the circulatory system. The major components of the fibrinolytic system, plasminogen and plasminogen activator, are known to co-exist in the blood but the biochemical details of how the proteolytic system is regulated to restrict plasmin formation to the sites of fibrin clots are not well understood. A possible mechanism of regulation involves the complexation of plasminogen with fibrin. To investigate the relevance of such a mechanism, the binding of Glu-plasminogen and Lys-plasminogen to fibrin, to immobilized lysine and to plasmin-cleaved fibrin were quantitatively characterized. The effects of two forms of fibrin on the activation kinetics of Glu- and Lys-plasminogen were also studied. The binding studies were performed using radioisotopically labelled plasminogen. A synthetic, fluorogenic substrate for plasmin was employed in the kinetic studies. Both forms of plasminogen displayed a physiologically relevant affinity for fibrin and limited plasmic cleavage of fibrin created new binding sites for plasminogen. This plasmin-created site is probably indentical to the functional moiety found on lysine-Sepharose. Fibrin possessed the capacity to significantly stimulate Glu-plasminogen activation by urokinase. A large decrease in the Michaelis constant (K(,m)) for activation occurred in the presence of fibrin, which in the lower, physiological range of Glu-plasminogen concentrations resulted in an enhanced rate of activation.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biochemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2014

Author dc:creator

• Bok, Robert Arnold

• Chemistry, Biochemistry

Identifier

(UMI)AAI8502073

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/70535