Platelet-vessel wall interactions in atherosclerotic disease

Abstract

SummaryDuring the prolonged course of atherosclerotic disease,platelets areofcentral importanceastheycontribute to the initiation of the disease,toi ts progressiona nd acutee xacerbation but also providep otentialr egenerativem echanisms. Platelets secrete chemokinesa nd cytokinest hatm ediatev ascular inflammation andare in turn activated by substances released from cells of the vascularwall.These interactions represent positive andnegative feedback loops, whichincaseofdysregulationmay lead to development andp rogression of disease.Furthermore, platelet adhesion to the endothelium is critical forthe initiation of atherosclerotic lesion formation in vivo.Evenp rior to endotheliald enudation, plateletadhesion governed by disturbedflowatpredilection sites foratherosclerosisinduces recruitment of proatheKeywords Atherothrombosis, plateletphysiology, stemcells rosclerotic cells andrelease of proinflammatory mediators from allinvolved cell types.Finally, the pathogenetic role of platelets for late atheroclerotic eventsincluding plaque rupture,microembolism or spasms withint he microcirculationi sw elle stablished. However, increasing evidence indicatesthatplatelets mediateon the other hand potential regenerativemechanisms. Platelets recruit circulating progenitor cells to sites of vasculari njury. Furthermore,theyinfluencetheir biological activity andmaturation. Therefore,platelets contribute at allstages of vasculardiseaseby interfering with highlyd ynamic processes. Understanding interactions of plateletswith othercirculatingcells andt he vascular wall is aprerequisite to understand cardiovascular disease andto identify potentialtherapeutic targets.

Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

“…In contrast, we observed a robust increase in adhesivity of murine and human melanoma cells in the presence of platelets in various settings in vitro. Adherent platelets present potent adhesion receptors such as JAM-C, P-Selectin, GPIb␣, or GPIIb/IIIa to other circulating cells providing a platform for a potent cellular bridging mechanism to the vascular wall (20,25,(52)(53)(54)(55)(56). Recently, glycoprotein Ib␣ (GPIb␣), the second most abundant receptor expressed on platelets, has been reported to be significantly involved in melanoma metastasis, as the functional absence of GPIb␣ correlated with a clear reduction in the number of lung metastatic foci in vivo (57).…”

Association between mean platelet volume and coronary artery calcification in patients without overt cardiovascular disease: an observational study

“…Platelets secrete chemokines and cytokines that mediate vascular inflammation and are in turn activated by substances released from cells of the vascular wall (15). Activated platelets stimulate thrombus formation in response to rupture of an atherosclerotic plaque or endothelial cell erosion, promoting atherothrombotic disease (16).…”

Plaque, Platelets, and Plug – The Pathogenesis of Acute Coronary Syndrome

“…P-selectin-mediated loose contact is subsequently changed by tighter connection involving endothelial cell integrin, v 3 and platelet integrin, IIb 3 (Langer & Gawaz, 2008). Ligation of platelet GPIb to endothelial cell von Willebrand factor during platelet rolling lead to activation of platelet integrin (Kasirer-Friede et al, 2002).…”