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POTENTIAL ROLE OF CIRCULATING PROGENITOR CELLS IN

CORONARY MICROVASCULAR DYSFUNCTION OF HEART TRANSPLANT

PATIENTS WITH NORMAL CORONARY ANGIOGRAMS

E. Osto, F. Tona, G.P. Fadini, G. Tarantini, I. Baesso, M. Napodano, C. Agostini,

A. Avogaro, G. Gerosa, S. Iliceto

University of Padova, Padova, Italy



We assessed the relationship between progenitor cells (PCs) and coronary microvascular

function in heart transplant (HT) patients (pts) with normal coronary angiograms.

Methods: We studied 41 pts (36 M, aged 50 ± 12 years) at 6 ± 3 years from HT and 40

age and sex matched healthy subjects. Six subpopulations of PCs were determined by

flow cytometry as follows: uncommitted (CD34+, CD133+, CD34+CD133+) and

endothelial PCs (EPCs, CD34+KDR+, CD133+KDR+, CD34+CD133+KDR+).

Coronary flow velocity in the LAD was detected at rest and during i.v. adenosine by

transthoracic echocardiography. Coronary flow reserve (CFR) was the ratio of hyperemic

diastolic velocity (DMV) to resting DMV. CFR <2.5 was considered abnormal. CFR was

measured in 10 pts (8 M, aged 50 ± 12 years) and was abnormal in 3 (group A) and

normal in 7 (group B).

Results: EPCs were lower in pts (p<0.05). CD34+ cell count was higher in group A than

in group B (583 ± 100 vs 282 ± 185 cells/10^6 cytometric events, p=0.01). CD34+ cell

count was also inversely correlated with CFR as shown in the figure. At multivariable

analysis, adjusted for time from HT, diabetes, hypertension and hypertrophy, CD34+ cell

count was the only independent predictor of CFR (beta=-0.773, p=0.006).

Conclusion: EPCs were reduced in HT pts with normal angiograms, in keeping with their

immunosuppressed status. Levels of CD34+ cells were inversely related with CFR.

Mobilization of uncommitted PCs may be involved in the pathogenesis of CAV, possibly

by PCs capacity of differentiation into neointimal and medial cells.



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