Role of platelet-derived microparticles in angiogenesis and tumor progression.

Platelets are key players in hemostasis, but are also involved in fundamental processes of vascular biology such as angiogenesis, tissue regeneration, and tumor metastasis. Microparticles (MP) are small plasma membrane vesicles shed from cells upon their activation or apoptosis. Platelet-derived microparticles (PMP) constitute the majority of the pool of MP circulating in the blood. In this review we will summarize some possible roles of PMP other than participation in blood coagulation. PMP can express and transfer functional receptors from platelet membranes, increase expression of adhesion molecules on cells, stimulate the release of cytokines, activate intracellular signaling pathways, alter vascular reactivity, induce angiogenesis, and are involved in cancer metastasis. The role of PMP in cancer development is unknown but a high PMP level is highly correlated with aggressive tumors and a poor clinical outcome. It has been reported that PMP can stimulate proliferation and adhesion of cancer cells. Given their documented association with pathological conditions, PMP may serve as biomarkers for disease status or as a possible new target for anti-platelet drugs to treat cancer or inflammation. On the other hand, local PMP application may be found useful for developing novel therapeutic strategies targeting angiogenesis-related conditions.

Frontiers in platelet inhibition.

Anti-platelet drugs play a key role in cardiovascular medicine since the introduction of aspirin as an anti-thrombotic agent some 50 years ago. After many years of a "monopoly" of aspirin, ADP receptor P2Y12 inhibitors were introduced with a significant improvement in clinical outcome. Nowadays dual anti-platelet therapy is the common practice for both acute events and secondary prevention in selected groups of patients. The improved efficacy of multiple drug therapy is associated with an increased risk of bleeding, which raises the issue of the dosing of these drugs. Recently, numerous studies have reported a variable laboratory response to aspirin and clopidogrel, which correlates with clinical outcome. Several mechanisms for causing this variable response have been proposed, including genetic variability, disease burden, and others. A major obstacle in this field is the lack of a standardized method for testing these responses. New drugs are currently under different stages of development, including new P2Y12 receptors inhibitors, thrombaxane receptor blockers, direct thrombin inhibitors, and inhibitors for other signaling pathways including oral GPIIbIIIa inhibitors. Thus anti-platelet therapy is currently under intensive developments toward multiple drug therapy and personal dose adjustment, which may improve clinical outcome.