Increased tissue factor expression predicts development of cardiac allograft vasculopathy.
BACKGROUND
Cardiac allograft vasculopathy (CAV) limits the long-term success of cardiac transplantation. The incidence of CAV is increased in patients with elevated plasma levels of oxidized lipids or fibrin deposition within right heart biopsy (RHB) specimens. The present study investigated whether tissue factor (TF), the expression of which is regulated by oxidized lipids, is upregulated in patients with CAV.


RESULTS
A TF score was developed to quantify TF expression in RHB specimens from 63 consecutive patients undergoing routine annual posttransplantation RHB and coronary angiography. In patients >2 years (3.0+/-0.8 years) posttransplantation (n=35), a high TF score was observed with greater frequency (75% versus 26%, P<0.004) in patients with CAV than those without CAV. In patients <2 years (0.87+/-0.48 years) posttransplantation (n=28) without evidence of CAV, the TF score was determined and patients were followed up prospectively. A high TF score had a positive predictive value of 78.6% for the development of CAV, and a low TF score had a negative predictive value of 100%.


CONCLUSIONS
These data demonstrate that early TF expression predicts subsequent development of CAV. Increased TF expression could link the elevated levels of oxidized LDL and fibrin deposition known to precede CAV. These findings suggest that TF may play a role in the pathophysiology of CAV and could offer a potential prognostic tool and a novel target for the prevention of CAV, possibly with antioxidants or inhibitors of the TF pathway.
Yen
Michael H
MH
Department of Cardiovascular Medicine, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
Pilkington
Guy
G
Starling
Randall C
RC
Ratliff
Norman B
NB
McCarthy
Patrick M
PM
Young
James B
JB
Chisolm
Guy M
GM
Penn
Marc S
MS
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D005500:Follow-Up Studies; D016027:Heart Transplantation; D006801:Humans; D011379:Prognosis; D013925:Thromboplastin / Q000096:biosynthesis*
D015415:Biomarkers; D013925:Thromboplastin