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Mobilization of sca1/flk-1 positive endothelial progenitor cells declines in apolipoprotein E-deficient mice with a high-fat diet.

Abstract：

BACKGROUND:Atherosclerosis features a deterioration of the endothelial layer in all stages. Restoration of the endothelium is associated with circulating stem cell antigen 1 (sca1) and vascular endothelial growth factor receptor type 2 (flk-1) positive endothelial progenitor cells (EPCs). We investigated whether EPC production and/or a mobilization from bone marrow are reduced in severe atherosclerosis. METHODS AND RESULTS:EPCs in peripheral blood were diminished in ApoE-/- mice with high-fat diet (HFD) whereas bone marrow levels of these cells were not significantly altered compared to controls. In situ perfusion of the hind limbs demonstrated that EPC mobilization was reduced compared to ApoE-/- mice with normal chow, although increased plasma stromal cell-derived factor (SDF) 1α and responsivity suggested a mobilizing stimulus. The proliferation of sca1/flk-1 positive cells showed no functional impairment. EPCs could not only be significantly mobilized from the bone marrow through the application of granulocyte colony stimulating factor (GCSF), but also led by trend to a depletion of the bone marrow pool. GCSF levels in plasma were equal in ApoE-/- mice with normal chow or HFD, which excluded a decline in GCSF production. CONCLUSION:The capability of the bone marrow pool to adapt the proliferation and mobilization of sca1/flk-1 positive EPCs seems overstrained in ApoE-/- mice with a HFD.

journal_name

J Cardiol

journal_title

Journal of cardiology

authors

Steinmetz M,Lucanus E,Zimmer S,Nickenig G,Werner N

doi

10.1016/j.jjcc.2015.02.008

subject

Has Abstract

pub_date

2015-12-01 00:00:00

pages

532-8

issue

6

eissn

0914-5087

issn

1876-4738

pii

S0914-5087(15)00058-1

journal_volume

66

pub_type

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