TY - JOUR
T1 - Differentiation of bone marrow-derived endothelial progenitor cells is shifted into a proinflammatory phenotype by hyperglycemia
AU - Loomans, Cindy J. M.
AU - van Haperen, Rien
AU - Duijs, Jacques M.
AU - Verseyden, Caroline
AU - de Crom, Rini
AU - Leenen, Pieter J. M.
AU - Drexhage, Hemmo A.
AU - de Boer, Hetty C.
AU - de Koning, Eelco J. P.
AU - Rabelink, Ton J.
AU - Staal, Frank J. T.
AU - van Zonneveld, Anton Jan
PY - 2009/5
Y1 - 2009/5
N2 - Bone marrow (BM)-derived endothelial progenitor cells (EPC) contribute to vascular maintenance by participating in angio- genesis, re-endothelialization, and remodeling. Myeloid progenitor cells in the BM are functionally and quantitatively an important precursor pool for cells that contribute to these processes. However, these precursor pools in the BM also give rise to important effector cells of the innate immune system, such as macrophages and dendritic cells. We hypothesized that the disturbed repair responses that are being observed in diabetes mellitus are also related to an effect on functional and differentiation characteristics at the level of this bone marrow precursor pool. Indeed, we observed that bone marrow differentiation cultures for EPC, macrophages (Mph), or dendritic cells (DC) from hyperglycemic BM yielded 40% fewer EPC and 50% more Mph compared with control BM. These changes were directly related to the hemoglobin A1C levels of the donor mice. BM-derived DC numbers were not affected by hyperglycemia.The composition of the BM was not altered; in particular, the numbers of CD31+/Ly6C+ cells, which serve as common progenitors for EPC,Mph,and DC,were unaffected. In addition,BM-derived EPC from hyperglycemic mice were less angiogenic and more proinflammatory in regards to endocytosis, T-cell activation, and interleukin 12 production. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibition by statin supplementation of the culture medium counteracted these hyperglycemia-induced changes. Our study results show that hyperglycemia alters the differentiation fate of BM precursor cells, reducing the potential to generate vascular regenerative cells and favoring the development of proinflammatory cells. © 2009 The Feinstein Institute for Medical Research.
AB - Bone marrow (BM)-derived endothelial progenitor cells (EPC) contribute to vascular maintenance by participating in angio- genesis, re-endothelialization, and remodeling. Myeloid progenitor cells in the BM are functionally and quantitatively an important precursor pool for cells that contribute to these processes. However, these precursor pools in the BM also give rise to important effector cells of the innate immune system, such as macrophages and dendritic cells. We hypothesized that the disturbed repair responses that are being observed in diabetes mellitus are also related to an effect on functional and differentiation characteristics at the level of this bone marrow precursor pool. Indeed, we observed that bone marrow differentiation cultures for EPC, macrophages (Mph), or dendritic cells (DC) from hyperglycemic BM yielded 40% fewer EPC and 50% more Mph compared with control BM. These changes were directly related to the hemoglobin A1C levels of the donor mice. BM-derived DC numbers were not affected by hyperglycemia.The composition of the BM was not altered; in particular, the numbers of CD31+/Ly6C+ cells, which serve as common progenitors for EPC,Mph,and DC,were unaffected. In addition,BM-derived EPC from hyperglycemic mice were less angiogenic and more proinflammatory in regards to endocytosis, T-cell activation, and interleukin 12 production. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibition by statin supplementation of the culture medium counteracted these hyperglycemia-induced changes. Our study results show that hyperglycemia alters the differentiation fate of BM precursor cells, reducing the potential to generate vascular regenerative cells and favoring the development of proinflammatory cells. © 2009 The Feinstein Institute for Medical Research.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=66449087109&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/19295918
U2 - https://doi.org/10.2119/molmed.2009.00032
DO - https://doi.org/10.2119/molmed.2009.00032
M3 - Article
C2 - 19295918
SN - 1076-1551
VL - 15
SP - 152
EP - 159
JO - Molecular Medicine
JF - Molecular Medicine
IS - 5-6
ER -