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CARDIOVASCULAR
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Volume 1, 1996, No 1 |
Abstract:
Background: This prospective longitudinal study was designed to
examine the relationship between the appearance of endothelial
activation and the development of coronary artery disease (CAD)
in transplanted human hearts. Methods: The study population was
81 allograft recipients who received the same immunosuppressive
therapy. The mean study time was 33.9 + 2.2 months per patient,
and annual angiograms on each graft were evaluated for the
development and/or progression of CAD. A total of 1147 biopsies
were obtained (14.2 + 0.5 biopsies per patient), and all biopsies
were evaluated for cellular infiltrates and endothelial
activation by using light microscopy and monoclonal antibody to
intercellular adhesion molecule-1 (ICAM-1 or CD54), respectively.
The activation marker was studied only on arterial and arteriolar
endothelium, because it is negative at these sites in time-zero
(i.e., pretransplantation) biopsies. Results: The
immunocytochemical data revealed that 19 of the allografts did
not develop ICAM-1 on arterial/arteriolar endothelium. The
angiographic data revealed only 2 diagnoses of CAD in the 19
grafts that failed to develop arterial/arteriolar ICAM-1, while
39 diagnoses of CAD were made in the 62 grafts that developed
arterial/arteriolar ICAM-1, yielding a high level of significance
(p=0.0001). Kaplan-Meier calculations also revealed a striking
association between the development of CAD and the per cent of
grafts with ICAM-1 reactivity of arterial/arteriolar endothelium.
Grafts without arterial/arteriolar ICAM-1 were free of CAD for
significantly longer periods of time (p=0.0005) compared with
grafts that developed ICAM-1 reactivity of arterial/arteriolar
endothelium. There was no significant association (p=0.21)
between ICAM-1 reactivity of arterial/arteriolar endothelium and
the number of histologically identified episodes of cellular
infiltrates. Conclusion: The results of this prospective study
thus reveal significant qualitative and quantitative associations
between the appearance of ICAM-1 (CD54) on arterial/arteriolar
endothelium and the subsequent development of CAD in transplanted
human hearts. This raises a question of whether endothelial
activation is a predisposing characteristic of spontaneous as
well as transplant-induced arteriopathies.
Keywords:
heart transplantation, arterial intercellular adhesion
molecule-1, coronary artery disease
Address for Correspondence:
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