David has long been interested in the response of the blood vessels to injury and the influence clotting and inflammation play in the ensuing proliferation and migration of vascular smooth muscle cells (VSMC) that may explain the reocclusion of vessels after percutaneous intervention. He proposed that an alternative physiological anticoagulant system, the product of which, activated protein C (aPC) could modulate the responses.
His research towards a Doctor of Medicine, awarded by Imperial College, London, in 2000, found a controllable level of anti-coagulation can be achieved if aPC when combined with low molecular weight heparin (LMWH). It bound to specific to sites on cultured human and rat vascular smooth muscle cells (VSMC) with properties similar to those described for the endothelial protein C receptor (EPCR). However, unlike the aPC/EPCR complex, the anticoagulant activity of aPC when bound to VSMC is maintained.
Furthermore, he also observed that the addition of aPC to VSMC enhances the activity of a number of mitogens. The expression of the putative receptor on VSMC may serve to protect the blood vessel from thrombosis and modulate the response and survival of cells following acute or chronic endothelial injury. This was presented in a plenary session at the International Society of Thrombosis and Haemostasis and led to a British Heart Foundation Grant.
David now works with a renowned Vascular Biology group at the University of Leeds. The research group have described molecular changes in blood vessels peculiar to patients with diabetes. The molecular mechanisms are being investigated and have been published