Impaired endothelial progenitor cell recruitment may contribute to heart transplant microvasculopathy.
BACKGROUND
Circulating progenitor cells (PCs) may play a role in the pathogenesis of cardiac allograft vasculopathy, the leading cause of morbidity and mortality in heart transplantation (HTx). We assessed the relationship between circulating PCs and their incorporation into allografts and coronary microvascular function in HTx.


METHODS
PCs were quantified by flow cytometry on the basis of the surface expression of CD34, CD133, and kinase domain receptor (KDR) antigens. Biopsy specimens at 2 different times were examined. Immunohistochemistry for the stem cell marker c-Kit, endothelial PC (EPC) marker KDR, and CD34 was performed in serial sections in all specimens. Cells positive for each marker were counted in all specimen area sections, and the number obtained was corrected by area section. Coronary flow in the left anterior descending coronary artery was detected at rest and during intravenous adenosine by transthoracic echocardiography. Coronary flow reserve (CFR) was the ratio of hyperemic diastolic mean velocity (DMV)/resting DMV.


RESULTS
CFR was measured in 29 patients and was abnormal (CFR < 2) in 6 (Group A) and normal in 23 (Group B). CFR was lower in Group A (1.5 ± 0.1 vs 3.3 ± 0.8, p < 0.0001). CD34(+)KDR(+), CD133(+)KDR(+), and CD34(+)CD133(+)KDR(+) cell counts were lower in Group A (p < 0.05). EPCs in biopsy sections tended to be lower in Group A (p = 0.06) and correlated to circulating CD133(+)KDR(+) and CD34(+)CD133(+)KDR(+) (p = 0.003 and p = 0.052, respectively).


CONCLUSIONS
EPCs are decreased in the circulation and in the allograft in patients with microvasculopathy. Defective mobilization and engraftment of EPCs may be involved in the pathogenesis of cardiac allograft vasculopathy.
Osto
Elena
E
Department of Cardiology, University of Padova, Padova, Italy.
Castellani
Chiara
C
Fadini
Gian Paolo
GP
Baesso
Ilenia
I
Gambino
Antonio
A
Agostini
Carlo
C
Avogaro
Angelo
A
Gerosa
Gino
G
Thiene
Gaetano
G
Iliceto
Sabino
S
Angelini
Annalisa
A
Tona
Francesco
F
D000071916:AC133 Antigen; D000328:Adult; D015703:Antigens, CD / Q000378:metabolism; D018952:Antigens, CD34 / Q000378:metabolism; D001783:Blood Flow Velocity; D002452:Cell Count; D002465:Cell Movement; D003326:Coronary Circulation; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D016027:Heart Transplantation / Q000009:adverse effects* / Q000473:pathology; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D010455:Peptides / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology*; D014184:Transplantation, Homologous; D014652:Vascular Diseases / Q000209:etiology* / Q000503:physiopathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; D040301:Vascular Endothelial Growth Factor Receptor-2