ATVB In Focus
Platelet Signal Transduction and Interactions With Vascular Cells
With this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, we begin a new series on the mechanisms of platelet activation and the interactions of platelets with other vascular cells. Because this is a vast topic, we have asked a group of active investigators to describe the work that they and others are doing in selected areas. The emphasis in each case is on topics in which new insights have been obtained recently. The series will include brief reviews on integrin structure and activation, granule exocytosis, reorganization of the platelet cytoskeleton, platelet activation by collagen, and the role of the GP Ib/IX/V complex. Additional reviews will cover adhesive interactions between platelets, leukocytes, and the vessel wall; new ideas about the varied role(s) of the platelet and endothelial cell adhesion molecule PECAM; the contribution of CD40L to platelet plug formation; and role of contact-dependent signaling during the late phases of platelet activation. A variety of viewpoints will be presented, emphasizing in each case areas of research that are still in a state of flux.
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For the first article in the series, Han-Mou Tsai1 at the Albert Einstein College of Medicine has contributed an excellent summary of the truly breakthrough work that he and other investigators have contributed in the past several years to understanding the pathogenesis of thrombotic thrombocytopenic purpura. TTP is (fortunately) an uncommon disorder in which platelet activation in the arterial circulation leads to obstruction of flow and downstream tissue damage. Unless treated aggressively, TTP is usually fatal. The studies summarized by Dr Tsai make a strong case that TTP arises from a failure of the normal proteolytic processing of von Willebrand factor–either because of a congenital absence of the required protease (ADAMTS13) or because of the acquisition of an inhibitor to the protease.
Although it may at first glance seem surprising to begin a series on the mechanisms of platelet activation with a review on disordered VWF processing, pathological platelet activation is for many of us at the heart of our interest in platelet biology. I hope that those of you who are new to this field will gain a sense of its continuing excitement and that those of you who are actively engaged in platelet research will find something new and, in some cases, controversial as well.