Dataset Information

Type 2 diabetes mellitus is associated with an imbalance in circulating endothelial and smooth muscle progenitor cell numbers.

ABSTRACT:

Aims/hypothesis

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/interpretation

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.

SUBMITTER: van Ark J

PROVIDER: S-EPMC3411291 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature

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Publications

Type 2 diabetes mellitus is associated with an imbalance in circulating endothelial and smooth muscle progenitor cell numbers.

van Ark J J Moser J J Lexis C P H CP Bekkema F F Pop I I van der Horst I C C IC Zeebregts C J CJ van Goor H H Wolffenbuttel B H R BH Hillebrands J L JL

Diabetologia 20120601 9

<h4>Aims/hypothesis</h4>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 diffe ...[more]

PMID: 22648662

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Project description:BACKGROUND:Within the last years, the interest in physical exercise as non-invasive stimulus influencing circulating hematopoietic stem and progenitor cell (CPC) concentrations has constantly grown. Cell estimates are often derived by determining the subgroup of CPC as percent lymphocytes (LYM) or mononuclear cells (MNC) via flow cytometry and back calculation over whole blood (WB) cell counts. However, results might depend on the used cell isolation technique and/or gating strategy. We aimed to investigate MNC loss and apoptosis during the flow cytometry sample preparation process preceded by either density gradient centrifugation (DGC) or red blood cell lysis (RBCL) and the potential difference between results derived from back calculation at different stages of cell isolation and from WB. METHODS:Human blood was subjected to DGC and RBCL. Samples were stained for flow cytometry analysis of CPC (CD34+/CD45dim) and apoptosis analysis (Annexin V) of MNC and CPC subsets. MNC and LYM gating strategies were compared. RESULTS:Both DGC as well as RBCL yielded comparable CPC concentrations independent of the gating strategy when back calculated over WB values. However, cell loss and apoptosis differed between techniques, where after DGC LYM, and monocyte (MONO) concentrations significantly decreased (p?<?0.01 and p?<?0.05, respectively), while after RBCL LYM concentrations significantly decreased (p?<?0.05) and MONO concentrations increased (p?<?0.001). LYM apoptosis was comparable between techniques, but MONO apoptosis was higher after DGC than RBCL (p?<?0.001). CONCLUSIONS:Investigated MNC counts (LYM/MONO ratio) after cell isolation and staining did not always mimic WB conditions. Thus, final CPC results should be corrected accordingly, especially when reporting live CPC concentrations after DGC; otherwise, the CPC regenerative potential in circulation could be biased. This is of high importance in the context of non-invasively induced CPC mobilization such as by acute physical exercise, since these cell changes are small and conclusions drawn from published results might affect further applications of physical exercise as non-invasive therapy.

Dataset Information

Type 2 diabetes mellitus is associated with an imbalance in circulating endothelial and smooth muscle progenitor cell numbers.

Aims/hypothesis

Methods

Results

Conclusions/interpretation

Publications

Type 2 diabetes mellitus is associated with an imbalance in circulating endothelial and smooth muscle progenitor cell numbers.

Similar Datasets

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