Current Projects - Platelet eicosanoids
When platelets are activated, as happens during the formation of thrombi, they release a large number of biologically active mediators. Many of these mediators are stored inside the platelets in granules ready for release. As well as these readily stored mediators, platelets also generate a set of mediators known as eicosanoids. Eicosanoids are made from the fatty acid arachidonic acid which is released from the platelet cell membranes by the actions of an enzyme called phospholipase A2. In collaboration with colleagues at Barts and the London Medical School, we have recently published a paper reporting two patients who uniquely lack the phospholipase A2 enzyme. The paper can be downloaded here.
One of the best known eicosanoids produced by activated platelets is thromboxane A2. It is the ability of aspirin to block the enzyme cyclooxygenase (which metabolises arachidonic acid towards thromboxane A2) that explains why aspirin is used to protect against heart attacks and strokes. In our current studies we are investigating further the full range of eicosanoids that can be produced by activated platelets. These products could be important to the development of both cardiovascular disease and various forms of cancer as you can see in our paper published in FASEBJ in 2015. We have also found human models of both loss of phospholipase A2 and platelet COX-1 that have added greatly to our understanding of these systems.
Our principal collaborators in this project are Prof. Jane Mitchell (Imperial College, London), Dr. Darryl Zeldin (NIEHS, NC, USA) and Dr. Ginger Milne (Vanderbilt University, TN, USA).
The slideshow displays some of this work.