Endothelial cell activation contributes to the release of procoagulant microparticles during acute cardiac allograft rejection.
BACKGROUND
Circulating procoagulant microparticles are reliable markers of vascular damage. The microparticle phenotypes provide additional information reflecting the nature of cell injury. This study assessed procoagulant microparticle levels and phenotypes in the diagnosis of acute allograft rejection after heart transplantation.


METHODS
Microparticles were prospectively investigated in the venous blood of 64 heart transplant patients, 23 with allograft rejection mainly of low score, and 41 without a rejection episode. Plasma concentrations of cytokines, cytoadhesins, and platelet activation markers were determined.


RESULTS
By univariate analysis, the mean time elapsed from heart transplant, cold ischemia time, E-selectin-, Fas- and tissue factor-bearing microparticles were associated with allograft rejection. By multivariate analysis, E-selectin-microparticle levels appeared independently associated with allograft rejection, even when other significant variables were included in the model (odds ratio, 9.8; 95% confidence interval, 1.36-71.4; p = 0.023).


CONCLUSIONS
The pattern of procoagulant microparticles released during acute allograft rejection suggests endothelial cell activation and Fas-mediated apoptosis. E-selectin-bearing microparticles appeared as an independent marker of acute allograft rejection that was still informative after adjustment for graft characteristics.
Morel
Olivier
O
Fédération de Cardiologie des Hôpitaux Universitaires de Strasbourg, France. olivier.morel@chrustrasbourg.fr
Ohlmann
Patrick
P
Epailly
Eric
E
Bakouboula
Babe
B
Zobairi
Fatiha
F
Jesel
Laurence
L
Meyer
Nicolas
N
Chenard
Marie-Pierre
MP
Freyssinet
Jean-Marie
JM
Bareiss
Pierre
P
Mazzucotelli
Jean-Philippe
JP
Toti
Florence
F
D000208:Acute Disease; D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D016207:Cytokines / Q000097:blood; D019040:E-Selectin / Q000097:blood*; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood* / Q000473:pathology; D016027:Heart Transplantation; D006801:Humans; D008297:Male; D008875:Middle Aged; D015539:Platelet Activation / Q000502:physiology*; D011379:Prognosis; D011446:Prospective Studies; D016024:Receptors, Cytoadhesin / Q000097:blood; D013925:Thromboplastin / Q000378:metabolism*; D014184:Transplantation, Homologous; D014461:Ultracentrifugation; D019014:fas Receptor / Q000097:blood*
D015415:Biomarkers; D016207:Cytokines; D019040:E-Selectin; C491901:FAS protein, human; D016024:Receptors, Cytoadhesin; D019014:fas Receptor; D013925:Thromboplastin