Thrombus Formation & Dissolution

Microvesicle involvement in the dynamics of thrombus formation and dissolution

Background:

The physiological response to a wound includes activation of the coagulation cascade, recruitment of specific cells and formation of a fibrin-rich meshwork (thrombus) to prevent excessive bleeding. Microvesicles are produced during activation of cells including platelets, endothelial cells and leukocytes. They have been shown to carry pro- and anti-coagulant/fibrinolytic proteins, and therefore may participate in maintaining haemostasis.

Aims:

Little is known about the role of microvesicles during thrombus formation, and therefore this PhD will assess:

1. The number, phenotype and location of microvesicles in a thrombus.
2. The effect of microparticles on clot formation and fibrinolysis.
3. The interaction of microvesicles, and the proteins and microRNA they carry, on endothelial cell-mediated haemostasis.
4. The mechanisms governing the contents of nascent microvesicles, with a view to manipulating microvesicle content for use as vectors in the future.

Potential clinical impact:

Increasing our knowledge of the role of microvesicles in the haemostatic response may help our understanding of health, as well as thrombosis and haemorrhagic disease. This research potentially provides a novel route for governing thrombus formation, through use of physiological or manufactured microvesicles as vectors for delivering coagulation therapy.

Methods to be used:

Immunohistochemistry, electron microscopy, coagulation assays, cell culture, flow cytometry, microRNA analysis, NMR.

Team Members involved: