TY - JOUR
T1 - Endothelial Progenitor Cell Dysfunction
T2 - A Novel Concept in the Pathogenesis of Vascular Complications of Type 1 Diabetes
AU - Loomans, Cindy J. M.
AU - de Koning, Eelco J. P.
AU - Staal, Frank J. T.
AU - Rookmaaker, Maarten B.
AU - Verseyden, Caroline
AU - de Boer, Hetty C.
AU - Verhaar, Marianne C.
AU - Braam, Branko
AU - Rabelink, Ton J.
AU - van Zonneveld, Anton-Jan
PY - 2004/1
Y1 - 2004/1
N2 - 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 HbA1c (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.
AB - 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 HbA1c (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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=9144271032&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/14693715
U2 - https://doi.org/10.2337/diabetes.53.1.195
DO - https://doi.org/10.2337/diabetes.53.1.195
M3 - Article
C2 - 14693715
SN - 0012-1797
VL - 53
SP - 195
EP - 199
JO - Diabetes
JF - Diabetes
IS - 1
ER -