Human endothelial progenitor cells from type II diabetics exhibit impaired proliferation, adhesion, and incorporation into vascular structures.
BACKGROUND
The recent discovery of circulating endothelial progenitor cells (EPCs) has altered our understanding of new blood vessel growth such as occurs during collateral formation. Because diabetic complications occur in conditions in which EPC contributions have been demonstrated, EPC dysfunction may be important in their pathophysiology.


RESULTS
EPCs were isolated from human type II diabetics (n=20) and age-matched control subjects (n=20). Proliferation of diabetic EPCs relative to control subjects was decreased by 48% (P<0.01) and inversely correlated with patient levels of hemoglobin A1C (P<0.05). Diabetic EPCs had normal adhesion to fibronectin, collagen, and quiescent endothelial cells but a decreased adherence to human umbilical vein endothelial cells activated by tumor necrosis factor-alpha (TNF-alpha) (P<0.05). In a Matrigel assay, diabetic EPCs were 2.5 times less likely to participate in tubule formation compared with controls (P<0.05).


CONCLUSIONS
These findings suggest that type II diabetes may alter EPC biology in processes critical for new blood vessel growth and may identify a population at high risk for morbidity and mortality after vascular occlusive events.
Tepper
Oren M
OM
Laboratory of Microvascular Research and Vascular Tissue Engineering, Institute of Reconstructive Plastic Surgery, New York University Medical Center, New York, NY 10016, USA.
Galiano
Robert D
RD
Capla
Jennifer M
JM
Kalka
Christoph
C
Gagne
Paul J
PJ
Jacobowitz
Glen R
GR
Levine
Jamie P
JP
Gurtner
Geoffrey C
GC
D000368:Aged; D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000254:growth & development* / Q000503:physiopathology; D002448:Cell Adhesion; D002454:Cell Differentiation; D002455:Cell Division; D002469:Cell Separation; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism / Q000502:physiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D005434:Flow Cytometry; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007511:Ischemia / Q000473:pathology / Q000628:therapy; D007797:Laminin / Q000502:physiology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic; D011509:Proteoglycans / Q000502:physiology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D003094:Collagen; D004338:Drug Combinations; D005353:Fibronectins; D006442:Glycated Hemoglobin; D007797:Laminin; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; C059485:matrigel