Levels of circulating endothelial progenitor cells are related to uremic toxins and vascular injury in hemodialysis patients.
BACKGROUND
Patients suffering from chronic kidney diseases (CKD) exhibit cardiovascular diseases and profound endothelial dysfunction. CKD patients have reduced numbers of endothelial progenitor cells, but little is known about the factors influencing these numbers.


OBJECTIVE
Among these factors, we hypothesized that uremic toxins and vascular injury affect endothelial progenitor cells.


METHODS
Thirty-eight hemodialysis patients were investigated and compared with 21 healthy controls. CD34+CD133+ immature progenitors, CD34+KDR+ endothelial progenitors cells (EPC) and myeloid EPC (mEPC) were counted in peripheral blood. Levels of uremic toxins beta(2)-microglobulin, indole-3 acetic acid, indoxylsulfate, p-cresylsulfate and homocysteine were measured. Vascular injury was assessed in hemodialysis (HD) patients by measuring aortic pulse wave velocity and plasma levels of endothelial microparticles. In vitro experiments were performed to study the effect of uremic toxins on apoptosis of progenitor cells.


CONCLUSIONS
CD34+CD133+ immature progenitor cell number was negatively correlated with the levels of uremic toxins beta(2)-microglobulin and indole-3 acetic acid. In vitro, indole-3 acetic acid induced apoptosis of CD133+ cells. These data indicate uremic toxins have a deleterious role on progenitor cells, early in the differentiation process. Moreover, mEPC number was positively correlated with markers of vascular injury-pulse wave velocity and endothelial microparticle levels. This suggests that vascular lesions could stimulate progenitor cell mobilization, even in a context of reduced EPC induced by CKD. In conclusion, uremic toxins and vascular injury appear to affect endothelial progenitor cell biology in CKD.
Jourde-Chiche
N
N
INSERM UMR 608, UFR Pharmacie, Université Aix-Marseille, Marseille.
Dou
L
L
Sabatier
F
F
Calaf
R
R
Cerini
C
C
Robert
S
S
Camoin-Jau
L
L
Charpiot
P
P
Argiles
A
A
Dignat-George
F
F
Brunet
P
P
D000071916:AC133 Antigen; D000368:Aged; D015703:Antigens, CD / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000096:biosynthesis; D017209:Apoptosis; D042783:Endothelial Cells / Q000166:cytology*; D005260:Female; D006023:Glycoproteins / Q000096:biosynthesis; D006801:Humans; D007210:Indoleacetic Acids / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000097:blood; D008297:Male; D008875:Middle Aged; D010455:Peptides; D006435:Renal Dialysis; D013234:Stem Cells / Q000166:cytology*; D014511:Uremia / Q000097:blood; D001613:beta 2-Microglobulin / Q000096:biosynthesis
D000071916:AC133 Antigen; D015703:Antigens, CD; D018952:Antigens, CD34; D006023:Glycoproteins; D007210:Indoleacetic Acids; C000606023:PROM1 protein, human; D010455:Peptides; D001613:beta 2-Microglobulin