Monomerization of C-reactive protein requires glycoprotein IIb-IIIa activation: pentraxins and platelet deposition

Pentraxins are inflammatory mediators linked to cardiovascular disease; however, their role in thrombosis remains to be fully elucidated.

We investigated the role of pentraxins in thrombus formation on different vascular substrates under flow conditions.

Native C-reactive protein (nCRP) and serum amyloid P (SAP) effects on thrombosis were evaluated under flow conditions on substrates placed in flat perfusion chambers. nCRP and dissociated monomeric CRP (mCRP) distributions were visualized by use of confocal microscopy. The effects of nCRP on vascular substrates were tested in the Badimon chamber.

mCRP, but not nCRP, induced a significant activation in platelet deposition, whereas SAP induced an activation only on fibrinogen-coated substrates. The effects of CRP on platelet deposition were significantly reduced by statin treatment. mCRP resulting from recirculation of blood containing nCRP over a thrombogenic vessel wall induced increased platelet deposition. Blocking glycoprotein IIb-IIIa prevented the effects of CRP dissociation and significantly reduced platelet deposition. Annexin V treatment did not block monomerization of CRP on activated platelets.

Under flow conditions, platelet deposited on all tested biological substrates support nCRP dissociation into mCRP. The effect is dependent on the thrombogenic potency of the substrate to trigger initial platelet deposition. Exposure of glycoprotein IIb-IIIa in the platelet surface supports nCRP dissociation. CRP monomerization was not dependent on the aminophospholipid exposed on the surface of activated platelets. The dissociated mCRP is trapped in the growing platelet aggregate and stimulates further platelet deposition. SAP increases platelet deposition only on fibrin monolayers. Therefore, pentraxins induce a platelet activation effect linking inflammation and thrombosis.