M. Merten et al., Platelet microparticles promote platelet interaction with subendothelial matrix in a glycoprotein IIb/IIIa-dependent mechanism, CIRCULATION, 99(19), 1999, pp. 2577-2582
Citations number
33
Categorie Soggetti
Cardiovascular & Respiratory Systems","Cardiovascular & Hematology Research
Background-Platelets, on activation, release vesicular particles called pla
telet microparticles. Despite their procoagulant activity, their functional
role in platelet-vessel wall interactions is not known.
Methods and Results-We examined the binding of microparticles to vessel wal
l components in vitro and in vivo. Microparticles bound to fibrinogen-, fib
ronectin-, and collagen-coated surfaces. Compared with activated platelets,
we observed minimal binding of microparticles to vitronectin and von Wille
brand factor, The glycoprotein IIb/IIIa (GP IIb/IIIa) inhibitors abciximab
and eptifibatide (Integrilin) inhibited the binding to fibrinogen and fibro
nectin but had minimal effect on binding to collagen. Furthermore, monoclon
al antibodies to GP Tt, or anionic phospholipid-binding proteins (beta(2)-g
lycoprotein I or annexin V) had no effect in these interactions. Microparti
cles did not bind to monolayers of resting or stimulated human umbilical ve
in endothelial cells (HUVECs), even in the presence of fibrinogen or von Wi
llebrand factor. However, under similar conditions, microparticles bound to
extracellular matrix produced by cultured HUVECs. Abciximab inhibited this
interaction by approximate to 50%. In a rabbit model of arterial endotheli
al injury, the infusion of Cr-51-labeled microparticles resulted in a 3- to
5-fold increase of microparticle adhesion to the injured site compared wit
h the uninjured site (P<0.05%). Furthermore, activated platelets bound to s
urface-immobilized microparticles in a GP IIb/IIIa-dependent mechanism. Thi
s binding increased in the presence of fibrinogen by approximate to 30%.
Conclusions-Platelet microparticles bind to subendothelial matrix in vitro
and in vivo and can act as a substrate for further platelet binding, This i
nteraction may play a significant role in platelet adhesion to the site of
endothelial injury.