End-stage renal disease causes an imbalance between endothelial and smooth muscle progenitor cells.
Patients with end-stage renal disease (ESRD) on hemodialysis have an increased risk of cardiovascular disease (CVD). Circulating endothelial progenitor cells (EPC) contribute to vascular regeneration and repair, thereby protecting against CVD. However, circulating smooth muscle progenitor cells (SPC) may contribute to adverse vascular remodeling. We hypothesized that an imbalance occurs between EPC and SPC in ESRD patients and sampled progenitor cells from 45 ESRD patients receiving regular treatment. Our study is the first to show reduced numbers of CD34+KDR+ hematopoietic stem cell (HSC)-derived EPC (type I EPC). Furthermore, monocyte-derived EPC cultured from mononuclear cells (type II EPC) were reduced in number and had a reduced capacity to stimulate endothelial cell angiogenesis. In contrast, SPC outgrowth was unaffected. In vitro incubation with uremic serum impaired type II EPC outgrowth from healthy donor mononuclear cells and did not influence SPC outgrowth. The hemodialysis procedure itself induced HSC apoptosis and caused an acute depletion of circulating EPC. Taken together, the decreased number and impaired function of EPC are compatible with impaired endogenous vascular repair in hemodialysis patients, whereas the unaffected SPC numbers suggest that the potential of progenitor cells to contribute to adverse remodeling is retained. This EPC-SPC imbalance may contribute to the acceleration of CVD in ESRD patients and could offer novel therapeutic targets.
Westerweel
Peter E
PE
Dept. of Vascular Medicine, F02.126, Univ. Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands.
Hoefer
Imo E
IE
Blankestijn
Peter J
PJ
de Bree
Petra
P
Groeneveld
Dafna
D
van Oostrom
Olivia
O
Braam
Branko
B
Koomans
Hein A
HA
Verhaar
Marianne C
MC
D018952:Antigens, CD34 / Q000032:analysis; D017209:Apoptosis; D042783:Endothelial Cells / Q000502:physiology*; D005260:Female; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis / Q000009:adverse effects; D013234:Stem Cells / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis
D018952:Antigens, CD34; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2