The Role of Platelets in Atherosclerosis: A Historical Review.

Atherosclerosis is a chronic, multifactorial inflammatory disorder of large and medium-size arteries, which is the leading cause of cardiovascular mortality and morbidity worldwide. Although platelets in cardiovascular disease have mainly been studied for their crucial role in the thrombotic event triggered by atherosclerotic plaque rupture, over the last two decades it has become clear that platelets participate also in the development of atherosclerosis, owing to their ability to interact with the damaged arterial wall and with leukocytes. Platelets participate in all phases of atherogenesis, from the initial functional damage to endothelial cells to plaque unstabilization.

Novel approaches to antiplatelet therapy.

Platelets are the main effectors of the thrombotic events occurring at a ruptured atherosclerotic plaque and therefore antiplatelet agents are the mainstay of antithrombotic treatment for the prevention of myocardial infarction, atherotrombotic ischemic stroke and critical limb ischemia due to the thrombotic occlusion of the peripheral arteries. Despite great progress in antiplatelet agents over the last two decades, a number of important unmet medical needs still remain, like insufficient efficacy and a high incidence of hemorrhagic complications. Advances in the knowledge of the molecular mechanisms regulating platelet participation in hemostasis and in thrombosis and progress in pharmaceutical design have allowed to identify new drugs for established antiplatelet targets and novel targets for the development of new agents.

Proline-rich tyrosine kinase Pyk2 regulates deep vein thrombosis.

Deep vein thrombosis results from the cooperative action of leukocytes, platelets, and endothelial cells. The proline-rich tyrosine kinase Pyk2 regulates platelet activation and supports arterial thrombosis. In this study, we combined pharmacological and genetic approaches to unravel the role of Pyk2 in venous thrombosis.