Abstract
Activated platelets may adhere to leukocytes and form circulating mixed aggregates.
The latter are considered a reliable marker of a prothrombotic state and are associated
with several cardiovascular conditions. The molecular mechanisms responsible of this
cellular interaction include a central role of platelet P-selectin and of P-selectin
glycoprotein ligand-1 (PSGL-1), its counter receptor on leukocytes in a signaling
cascade, resulting in the activation of the beta-2 integrin Mac-1 and in the firm
adhesion between the two cell types. The interaction of P-selectin with PSGL-1 also
induces upregulation of leukocyte tissue factor, biosynthesis of several cytokines
and other inflammatory reactions, thereby contributing to the thrombotic progression.
In this review the main determinants of mixed aggregate formation, the heritability
component, the major pathological conditions associated with higher levels of mixed
aggregates in the circulation will be discussed. Besides current anti-platelet or
antithrombotic drugs, natural compounds, such as the polyphenols present in vegetable
foods and red wine, have been tested for their inhibitory effect on mixed aggregate
formation. The promising results shown by studies in vitro and in experimental animal models, remain to be carefully investigated in humans.
Platelet–leukocyte aggregates provide a novel link between inflammation and thrombosis,
two central processes in atherogenesis. A better understanding of the role of platelet–leukocyte
interactions in athero-thrombosis will be instrumental for the progress of prevention
and treatment of ischaemic cardiovascular disease.
Keywords
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Article info
Publication history
Published online: November 11, 2011
Accepted:
October 13,
2011
Received in revised form:
October 12,
2011
Received:
September 24,
2011
Identification
Copyright
© 2011 Elsevier Ltd. Published by Elsevier Inc. All rights reserved.
