Type 2 diabetes mellitus is associated with an imbalance in circulating endothelial and smooth muscle progenitor cell numbers.
OBJECTIVE
Individuals with type 2 diabetes mellitus have increased rates of macrovascular disease (MVD). Endothelial progenitor cells (EPCs), circulating angiogenic cells (CACs) and smooth muscle progenitor cells (SMPCs) are suggested to play a role in the pathogenesis of MVD. The relationship between vasoregenerative EPCs or CACs and damaging SMPCs and the development of accelerated MVD in diabetes is still unknown. We tried to elucidate whether EPC, CAC and SMPC numbers and differentiation capacities in vitro differ in patients with and without diabetes or MVD.


METHODS
Peripheral blood was obtained from individuals with and without diabetes and MVD (coronary or peripheral artery disease). EPC and SMPC numbers were determined with flow cytometry. Furthermore, CAC and SMPC numbers were quantified after in vitro culture. Their in vitro differentiation capacity was investigated with real-time RT-PCR and quantitative immunofluorescence.


RESULTS
In diabetic patients both EPC and CAC levels were reduced (1.3-fold [p < 0.05] and 1.5-fold [p < 0.05], respectively). CAC outgrowth from diabetic patients with MVD was reduced 1.5-fold compared with diabetic patients without MVD (p < 0.05). SMPC levels were similar between diabetic patients and healthy controls. The CAC/SMPC ratio of in vitro cultured progenitor cells was reduced 2.3-fold in samples from diabetic patients (p < 0.001). The differentiation capacity of CACs and SMPCs in vitro remained similar independently of diabetes or MVD.


CONCLUSIONS
The ratio between EPCs or CACs and SMPCs is disturbed in type 2 diabetes in favour of SMPCs. This may translate into reduced vascular repair capacity, thereby promoting MVD in type 2 diabetes.
Department of Pathology & Medical Biology-Pathology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, PO Box 30.001, Groningen, the Netherlands.
J
J
van Ark
J
J
Moser
C P H
CP
Lexis
F
F
Bekkema
I
I
Pop
I C C
IC
van der Horst
C J
CJ
Zeebregts
H
H
van Goor
B H R
BH
Wolffenbuttel
J L
JL
Hillebrands
D000368:Aged; D016022:Case-Control Studies; D002454:Cell Differentiation; D002478:Cells, Cultured; D003324:Coronary Artery Disease / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D016491:Peripheral Vascular Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D013234:Stem Cells / Q000378:metabolism*