The Impact of Thrombus Composition on Regulation of Fibrinolysis Under Flow

Fibrin structure profoundly impacts a clots susceptibility to fibrinolysis with compact networks linked to early onset of coronary heart disease. Shear stress modulates the structure and cellular composition of thrombi in vivo, but most models of fibrinolysis do not account for flow. This project will develop a novel flow model which allows thrombus formation and lysis to be visualized in a single system. Using this novel model and our established Chandler model thrombi system, we will assess how shear rates that mimic venous and arterial circulation affect thrombus structure, composition and susceptibility to lysis. Using fluorescent confocal microscopy we will monitor movement of fibrinolytic proteases through thrombi of different compositions. In turn we will analyse how flow modulates lysis by plasminogen activators and clinically relevant thrombolytic agents.