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Annexin A5 multitasking: a potentially novel antiatherothrombotic agent?

Atherothrombosis, formed on an underlying atherosclerotic plaque, is the key pathogenic mechanism behind the majority of clinically evident cardiovascular ischemic diseases including acute coronary artery disease, cerebrovascular and peripheral arterial occlusion. Annexin A5 (ANXA5; previously annexin V), a member of the annexin superfamily, is a protein with potent and unique antithrombotic properties. The antithrombotic effect exerted by ANXA5 is thought to be mediated mainly by mechanical shielding of phospholipids, phosphatidylserine in particular, thereby reducing their availability for coagulation reactions. However, other intriguing properties of ANXA5 potentially contributing to its antithrombotic function, especially downregulation of surface expressed tissue factor, or interaction with additional ligands involved in hemostasis such as sulfatide and heparin, as well as upregulation of urokinase-type plasminogen activator were reported. The biological significance of ANXA5 as a member of endogenous antithrombotic system in vivo has been suggested recently for the large vasculature and for placental microcirculation. Antiatherothrombotic potential of ANXA5 deserves further attention and careful studies in order to determine its true physiological impact as well as its possible therapeutic applications.