Limits...
Reverse-D-4F Increases the Number of Endothelial Progenitor Cells and Improves Endothelial Progenitor Cell Dysfunctions in High Fat Diet Mice.

Nana Y, Peng J, Jianlin Z, Xiangjian Z, Shutong Y, Enxin Z, Bin L, Chuanlong Z, Hua T, Yanhong S, Yunsai D, Shucun Q, Hui W - PLoS ONE (2015)

Bottom Line: Although high density lipoprotein (HDL) improves the functions of endothelial progenitor cells (EPCs), the effect of HDL ApoAI mimetic peptide reverse-D-4F (Rev-D4F) on EPC mobilization and repair of EPC dysfunctions remains to be studied.However, it significantly increased the number of white blood cells, the percentage of monocytes in the white blood cells, and the level of vascular endothelial growth factor (VEGF) and TNF-α in the plasma.Our results suggested that Rev-D4F increases the quantity of endothelial progenitor cells through increasing the SDF-1α levels and decreasing the TNF-α level of peripheral blood in high fat diet-induced C57BL/6J mice, and restores TNF-α induced dysfunctions of EPCs partly through stimulating the PI3K/AKT signal pathway.

View Article: PubMed Central - PubMed

Affiliation: College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China; Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China.

ABSTRACT
Although high density lipoprotein (HDL) improves the functions of endothelial progenitor cells (EPCs), the effect of HDL ApoAI mimetic peptide reverse-D-4F (Rev-D4F) on EPC mobilization and repair of EPC dysfunctions remains to be studied. In this study, we investigated the effects of Rev-D4F on peripheral blood cell subpopulations in C57 mice treated with a high fat diet and the mechanism of Rev-D4F in improving the function of EPCs impaired by tumor necrosis factor-α (TNF-α). The high fat diet significantly decreased the number of EPCs, EPC migratory functions, and the percentage of lymphocytes in the white blood cells. However, it significantly increased the number of white blood cells, the percentage of monocytes in the white blood cells, and the level of vascular endothelial growth factor (VEGF) and TNF-α in the plasma. Rev-D4F clearly inhibited the effect of the high fat diet on the quantification of peripheral blood cell subpopulations and cytokine levels, and increased stromal cell derived factor 1α (SDF-1α) in the plasma. We provided in vitro evidence that TNF-α impaired EPC proliferation, migration, and tube formation through inactive AKT and eNOS, which was restored by Rev-D4F treatment. In contrast, both the PI3-kinase (PI3K) inhibitor (LY294002) and AKT inhibitor (perifosine) obviously inhibited the restoration of Rev-4F on EPCs impaired by TNF-α. Our results suggested that Rev-D4F increases the quantity of endothelial progenitor cells through increasing the SDF-1α levels and decreasing the TNF-α level of peripheral blood in high fat diet-induced C57BL/6J mice, and restores TNF-α induced dysfunctions of EPCs partly through stimulating the PI3K/AKT signal pathway.

No MeSH data available.


Related in: MedlinePlus

The proportion of different leukocyte subsets in mice blood.A, Representative of the number of white blood cells per liter. B, C, and D Monocytes, neutrophils, and lymphocytes in percentage of white blood cells, respectively. Data are presented as mean±SD (n = 6). **P <0.01.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4580448&req=5

pone.0138832.g004: The proportion of different leukocyte subsets in mice blood.A, Representative of the number of white blood cells per liter. B, C, and D Monocytes, neutrophils, and lymphocytes in percentage of white blood cells, respectively. Data are presented as mean±SD (n = 6). **P <0.01.

Mentions: Further analysis of the C57 mice peripheral blood indicated that Rev-D4F significantly decreased high fat diet-induced leukocytosis (Fig 4A). Among these leukocytes, the number of monocytes and neutrophils obviously increased in the high fat diet mice group compared with the chow diet group. Analysis of the peripheral blood in mice treated with Rev-D4F demonstrated that Rev-D4F obviously inhibited the high fat diet-induced increase in the numbers of leukocyte, neutrophils, and monocytes (Fig 4A–4C). In contrast, Rev-D4F significantly inhibited the peripheral blood lymphocyte reduction induced by the high fat diet (Fig 4D).


Reverse-D-4F Increases the Number of Endothelial Progenitor Cells and Improves Endothelial Progenitor Cell Dysfunctions in High Fat Diet Mice.

Nana Y, Peng J, Jianlin Z, Xiangjian Z, Shutong Y, Enxin Z, Bin L, Chuanlong Z, Hua T, Yanhong S, Yunsai D, Shucun Q, Hui W - PLoS ONE (2015)

The proportion of different leukocyte subsets in mice blood.A, Representative of the number of white blood cells per liter. B, C, and D Monocytes, neutrophils, and lymphocytes in percentage of white blood cells, respectively. Data are presented as mean±SD (n = 6). **P <0.01.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4580448&req=5

pone.0138832.g004: The proportion of different leukocyte subsets in mice blood.A, Representative of the number of white blood cells per liter. B, C, and D Monocytes, neutrophils, and lymphocytes in percentage of white blood cells, respectively. Data are presented as mean±SD (n = 6). **P <0.01.
Mentions: Further analysis of the C57 mice peripheral blood indicated that Rev-D4F significantly decreased high fat diet-induced leukocytosis (Fig 4A). Among these leukocytes, the number of monocytes and neutrophils obviously increased in the high fat diet mice group compared with the chow diet group. Analysis of the peripheral blood in mice treated with Rev-D4F demonstrated that Rev-D4F obviously inhibited the high fat diet-induced increase in the numbers of leukocyte, neutrophils, and monocytes (Fig 4A–4C). In contrast, Rev-D4F significantly inhibited the peripheral blood lymphocyte reduction induced by the high fat diet (Fig 4D).

Bottom Line: Although high density lipoprotein (HDL) improves the functions of endothelial progenitor cells (EPCs), the effect of HDL ApoAI mimetic peptide reverse-D-4F (Rev-D4F) on EPC mobilization and repair of EPC dysfunctions remains to be studied.However, it significantly increased the number of white blood cells, the percentage of monocytes in the white blood cells, and the level of vascular endothelial growth factor (VEGF) and TNF-α in the plasma.Our results suggested that Rev-D4F increases the quantity of endothelial progenitor cells through increasing the SDF-1α levels and decreasing the TNF-α level of peripheral blood in high fat diet-induced C57BL/6J mice, and restores TNF-α induced dysfunctions of EPCs partly through stimulating the PI3K/AKT signal pathway.

View Article: PubMed Central - PubMed

Affiliation: College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China; Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China.

ABSTRACT
Although high density lipoprotein (HDL) improves the functions of endothelial progenitor cells (EPCs), the effect of HDL ApoAI mimetic peptide reverse-D-4F (Rev-D4F) on EPC mobilization and repair of EPC dysfunctions remains to be studied. In this study, we investigated the effects of Rev-D4F on peripheral blood cell subpopulations in C57 mice treated with a high fat diet and the mechanism of Rev-D4F in improving the function of EPCs impaired by tumor necrosis factor-α (TNF-α). The high fat diet significantly decreased the number of EPCs, EPC migratory functions, and the percentage of lymphocytes in the white blood cells. However, it significantly increased the number of white blood cells, the percentage of monocytes in the white blood cells, and the level of vascular endothelial growth factor (VEGF) and TNF-α in the plasma. Rev-D4F clearly inhibited the effect of the high fat diet on the quantification of peripheral blood cell subpopulations and cytokine levels, and increased stromal cell derived factor 1α (SDF-1α) in the plasma. We provided in vitro evidence that TNF-α impaired EPC proliferation, migration, and tube formation through inactive AKT and eNOS, which was restored by Rev-D4F treatment. In contrast, both the PI3-kinase (PI3K) inhibitor (LY294002) and AKT inhibitor (perifosine) obviously inhibited the restoration of Rev-4F on EPCs impaired by TNF-α. Our results suggested that Rev-D4F increases the quantity of endothelial progenitor cells through increasing the SDF-1α levels and decreasing the TNF-α level of peripheral blood in high fat diet-induced C57BL/6J mice, and restores TNF-α induced dysfunctions of EPCs partly through stimulating the PI3K/AKT signal pathway.

No MeSH data available.


Related in: MedlinePlus