Endothelial progenitor cells are decreased in blood of cardiac allograft patients with vasculopathy and endothelial cells of noncardiac origin are enriched in transplant atherosclerosis.
BACKGROUND
Recent studies in animals suggest that circulating recipient endothelial precursors may participate in the biology of transplant vasculopathy. It is currently unknown whether a similar interaction between recipient endothelial cells and the vessel wall occurs in human subjects undergoing allogeneic cardiac transplantation.


RESULTS
Circulating endothelial cells and endothelial progenitor cells (EPCs) were quantified in 15 cardiac transplantation subjects with and without angiographic evidence of vasculopathy. In a separate series of experiments, the origin (donor or recipient) of transplant plaque endothelial cells was assessed in subjects who had undergone a gender-mismatched cardiac transplantation and had histological evidence of severe vasculopathy at the time of heart explantation. Circulating EPC outgrowth colonies in peripheral blood were significantly reduced in subjects with transplant vasculopathy compared with those without angiographic evidence of disease (EPC colony-forming units [CFUEPC]: 4.5+/-1.9 versus 15.1+/-3.7, P<0.05). There was no significant difference in circulating endothelial cell numbers as defined by day 4 culture acetylated LDL/lectin assay in either of these patient groups. In a separate group of 5 subjects who underwent gender-mismatched cardiac transplantation, there was a significant seeding of recipient endothelial cells (range: 1% to 24% of all luminal endothelial cells) in large-vessel lumen and adventitial microvessel lumen of arteriopathic vessels. No opposite-sex chimeric cells were observed in control gender-matched transplantation scenarios.


CONCLUSIONS
These data suggest that the human cardiac transplant arteriopathy is associated with reduction in circulating endothelial precursors and with seeding of recipient-derived endothelial cells at the site of plaque development.
Simper
David
D
Division of Cardiovascular Diseases and Molecular Medicine Program, Mayo Clinic, Rochester, Minn 55905, USA.
Wang
Shaohua
S
Deb
Arjun
A
Holmes
David
D
McGregor
Christopher
C
Frantz
Robert
R
Kushwaha
Sudhir S
SS
Caplice
Noel M
NM
D000328:Adult; D015703:Antigens, CD / Q000032:analysis; D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*; D001158:Arteries / Q000473:pathology; D001161:Arteriosclerosis / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D002452:Cell Count; D019070:Cell Lineage; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000473:pathology* / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D016027:Heart Transplantation / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D012016:Reference Values; D012737:Sex Factors; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology; D018183:Transplantation Chimera
D015703:Antigens, CD