C-reactive protein isoforms differ in their effects on thrombus growth.
OBJECTIVE
We studied the impact of native (natCRP) and modified CRP (mCRP) isoforms on platelet adhesion and thrombus growth under arterial flow.


RESULTS
Blood was perfused over type I collagen at a wall shear rate of 1500 s(-1), and platelet deposition and thrombus growth were evaluated by confocal microscopy. natCRP and mCRP were either incubated with blood before perfusion experiments or immobilized in the collagen surface and exposed to flowing blood. mCRP significantly increased platelet adhesion and thrombus growth when directly incubated with blood and when immobilized on a collagen surface (P<0.05). In contrast, natCRP did not exert any effect. Confocal immunohistochemistry revealed the presence of CRP on the surface of adhered platelets and within the thrombus and showed an upregulation of P-selectin and CD36 in effluent platelets preincubated with mCRP (P<0.05). Flow cytometry analysis of agonist-induced platelet activation demonstrated that mCRP, but not natCRP, significantly increased platelet surface P-selectin (P<0.05) without modifying CD63 and PAC-1.


CONCLUSIONS
Our data indicate that whereas serum natCRP may not affect thrombus growth, mCRP displays a prothrombotic phenotype enhancing not only platelet deposition, but also thrombus growth under arterial flow conditions.
Molins
Blanca
B
Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Peña
Esther
E
Vilahur
Gemma
G
Mendieta
Carlos
C
Slevin
Mark
M
Badimon
Lina
L
D002097:C-Reactive Protein / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology; D018955:CD36 Antigens / Q000097:blood; D020099:Coated Materials, Biocompatible; D006801:Humans; D066298:In Vitro Techniques; D018613:Microscopy, Confocal; D019007:P-Selectin / Q000097:blood; D010477:Perfusion; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000737:chemistry / Q000494:pharmacology / Q000502:physiology; D013927:Thrombosis / Q000097:blood / Q000209:etiology* / Q000473:pathology
D018955:CD36 Antigens; D020099:Coated Materials, Biocompatible; D019007:P-Selectin; D020033:Protein Isoforms; D002097:C-Reactive Protein