Title:Platelets in Thrombosis and Hemostasis: Old Topic with New Mechanisms
Volume: 12
Issue: 2
Author(s): Yiming Wang, Marc Andrews, Yan Yang, Sean Lang, Joseph W. Jin, Alison Cameron- Vendrig, Guangheng Zhu, Adili Reheman and Heyu Ni
Affiliation:
Keywords:
GPIb complex, von Willebrand factor, integrins, integrin ligands, platelets, thrombosis, hemostasis
Abstract: Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. After being released
into the circulation, platelets play key roles in the surveillance of vascular injury, and can quickly adhere and aggregate at
the site of injury, which are critical events for vascular repair and hemostasis. However, the same biological processes of
platelet adhesion and aggregation may also cause thrombotic disorders. The formation of a platelet plug at sites of
atherosclerotic lesion rupture is the most common mechanism leading to myocardial or cerebral infarction. Platelet-related
deep vein thrombosis is also one of the leading causes of mortality worldwide. The contribution of several platelet
receptors and their ligands has been highlighted in these processes. In platelet adhesion, particularly at high shear stress,
GPIbα-von Willebrand factor (VWF) interaction may initiate this event, which is followed by GPVI signalling and firm
platelet adhesion mediated by members of the integrin family, such as β3 (αIIbβ3) and β1 (α2β1, α5β1) integrins. In
platelet aggregation, although GPIbα-VWF, P selectin-sulfatides, and other molecules, may be involved, the process is
mainly mediated by β3 (αIIbβ3) integrin and its ligands, such as fibrinogen and VWF. It is intriguing that platelet
adhesion and aggregation still occur in mice lacking both fibrinogen and VWF, suggesting that other unforeseen
molecule(s) may also be important in these processes. Identification and characterization of these molecules will enrich
our knowledge in the basic science of hemostasis and thrombosis, and may lead to the development of new therapies
against bleeding disorders and thrombotic diseases.
