Regulation Of Platelet Formation Research Articles

Role of β1 integrin in thrombocytopoiesis.

Thrombocytopoiesis is a complex process beginning at the level of hematopoietic stem cells, which ultimately generate megakaryocytes, large marrow cells with a distinctive morphology, and then, through a process of terminal maturation, megakaryocytes shed thousands of platelets into the circulation. This process is controlled by intrinsic and extrinsic factors. Emerging data indicate that an important intrinsic control on the late stages of thrombopoiesis is exerted by integrins, a family of transmembrane receptors composed of one α and one β subunit. One β subunit expressed by megakaryocytes is the β1 integrin, the role of which in the regulation of platelet formation is beginning to be clarified. Here, we review recent data indicating that activation of β1 integrin by outside-in and inside-out signaling regulates the interaction of megakaryocytes with the endosteal niche, which triggers their maturation, while its inactivation by galactosylation determines the migration of these cells to the perivascular niche, where they complete their terminal maturation and release platelets in the bloodstream. Furthermore, β1 integrin mediates the activation of transforming growth factor β (TGF-β), a protein produced by megakaryocytes that may act in an autocrine fashion to halt their maturation and affect the composition of their surrounding extracellular matrix. These findings suggest that β1 integrin could be a therapeutic target for inherited and acquired disorders of platelet production.

Platelet Turnover in Atherothrombotic Disease

Platelets play a pivotal role in primary hemostasis where their rapid response to vascular injury prevents excessive bleeding. To accomplish this, platelets are enriched in membrane receptors and cytoplasmic enzymes with often redundant and self-amplifying functions leading to platelet activation, release into the bloodstream of hemostatically active compounds and culminating with thrombus formation. However, the same process in the pathological state of atherosclerosis can lead to thrombotic complications such as an acute coronary syndrome or stroke. The role of platelets in this process is more extensive than previously believed. Several lines of evidence suggest that platelets contribute not only to the acute thrombotic events in atherosclerosis, but also to disease initiation and progression. This review focuses on the role of platelet heterogeneity and turnover in atherothrombotic disease. Specifically, this article covers (a) the regulation of platelet formation; (b) the role of the heterogeneity of platelets in atherothrombotic diseases; (c) the disease-modifying effect of platelets on the development of atherosclerosis; and (d) the modifying effect of atherosclerotic disease on platelet production and function; (e) the platelet indices influencing platelet responsiveness to antiplatelet therapies; and finally (f) the potential novel therapeutic modalities that could be applied in atherothrombosis.