title: Endothelial progenitor cell dysfunction: a novel concept in the pathogenesis of vascular complications of type 1 diabetes.
abstract: Type 1 diabetes is associated with reduced vascular repair, as indicated by impaired wound healing and reduced collateral formation in ischemia. Recently, endothelial progenitor cells (EPCs) have been identified as important regulators of these processes. We therefore explored the concept that EPCs are dysfunctional in diabetes. The number of EPCs obtained from type 1 diabetic patients in culture was 44% lower compared with age- and sex-matched control subjects (P < 0.001). This reduction was inversely related to levels of HbA(1c) (R = -0.68, P = 0.01). In addition, we demonstrated that patient EPCs were also impaired in function using an in vitro angiogenesis assay. Conditioned media from patient EPCs were significantly reduced in their capacity to support endothelial tube formation in comparison to control EPCs. Therefore, despite culturing the EPCs under normoglycemic conditions, functional differences between patient and control EPCs were maintained. Our findings demonstrate that adverse metabolic stress factors in type 1 diabetes are associated with reduced EPC numbers and angiogenicity. We hypothesize that EPC dysfunction contributes to the pathogenesis of vascular complications in type 1 diabetes.
authors.affiliation: Department of Vascular Medicine and Diabetology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Cindy J M
authors.initials: CJ
authors.lastname: Loomans
authors.forename: Eelco J P
authors.initials: EJ
authors.lastname: de Koning
authors.forename: Frank J T
authors.initials: FJ
authors.lastname: Staal
authors.forename: Maarten B
authors.initials: MB
authors.lastname: Rookmaaker
authors.forename: Caroline
authors.initials: C
authors.lastname: Verseyden
authors.forename: Hetty C
authors.initials: HC
authors.lastname: de Boer
authors.forename: Marianne C
authors.initials: MC
authors.lastname: Verhaar
authors.forename: Branko
authors.initials: B
authors.lastname: Braam
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.forename: Anton-Jan
authors.initials: AJ
authors.lastname: van Zonneveld
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000473:pathology*; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000473:pathology*; D012016:Reference Values; D013234:Stem Cells / Q000473:pathology*
chemical_list: D006442:Glycated Hemoglobin