title: Progenitor cells and vascular function are impaired in patients with chronic kidney disease.
abstract: BACKGROUND
  Endothelial dysfunction contributes to accelerated atherosclerosis in chronic kidney disease (CKD). Bone marrow-derived endothelial progenitor cells (EPC) constitute an endogenous vascular repair system protecting against atherosclerosis. Smooth muscle progenitor cells (SPC) may stimulate atherosclerosis development. We hypothesized that an imbalance in EPC and SPC occurs in CKD, which may contribute to the increased cardiovascular disease (CVD) risk.
  
  
  METHODS
  EPC and SPC outgrowth from mononuclear cells (MNC), EPC migratory function and circulating CD34(+)KDR(+)-EPC were measured in 49 patients with varying degrees of CKD on regular therapy and 33 healthy volunteers. Renal function, CKD cause, CVD history and endothelial dysfunction parameters were determined as factors of influence on progenitor cells.
  
  
  RESULTS
  Patients had reduced EPC outgrowth compared to controls [9 (2-22) vs 12 (1-38) cells/10(3) MNC, P = 0.026], independent of CKD cause and degree, whereas SPC outgrowth levels were higher in patients with more impaired kidney function (r = -0.397, P = 0.008). Patients had lower CD34(+)KDR(+)-EPC compared to controls [9 (0-52) vs 19 (4-110) cells/10(5) granulocytes, P = 0.004]. CVD history and increased endothelial dysfunction markers were related to lower EPC levels. Progenitor cell outgrowth was shifted towards SPC with progression of endothelial damage. Reduction in EPC could not be attributed to decreases in progenitor cell-mobilizing factors SDF-1 alpha and VEGF as levels increased with progressive kidney and endothelial dysfunction, while EPC remained low.
  
  
  CONCLUSIONS
  Our data suggest that, already in mild CKD, EPC-mediated endogenous vascular regeneration is impaired, while SPC levels increase with declining kidney function.
authors.affiliation: Department of Nephrology and Hypertension, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Kim E
authors.initials: KE
authors.lastname: Jie
authors.forename: Masha A
authors.initials: MA
authors.lastname: Zaikova
authors.forename: Marloes W T
authors.initials: MW
authors.lastname: Bergevoet
authors.forename: Peter E
authors.initials: PE
authors.lastname: Westerweel
authors.forename: Mehdi
authors.initials: M
authors.lastname: Rastmanesh
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Blankestijn
authors.forename: Walther H
authors.initials: WH
authors.lastname: Boer
authors.forename: Branko
authors.initials: B
authors.lastname: Braam
authors.forename: Marianne C
authors.initials: MC
authors.lastname: Verhaar
mesh_terms: D000328:Adult; D053687:Adult Stem Cells / Q000473:pathology*; D000368:Aged; D000369:Aged, 80 and over; D050197:Atherosclerosis / Q000209:etiology; D001854:Bone Marrow Cells / Q000473:pathology; D002318:Cardiovascular Diseases / Q000209:etiology; D016022:Case-Control Studies; D054377:Chemokine CXCL12 / Q000097:blood; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D032390:Myoblasts, Smooth Muscle / Q000473:pathology; D012038:Regeneration; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A