title: Reverse-D-4F Increases the Number of Endothelial Progenitor Cells and Improves Endothelial Progenitor Cell Dysfunctions in High Fat Diet Mice.
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.
authors.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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Nana
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Jiao
authors.initials: J
authors.lastname: Peng
authors.affiliation: Central Hospital of Taian, Taian, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Jianlin
authors.affiliation: Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease and Hebei Key Laboratory of Vascular Homeostasis, Shijiazhuang, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Xiangjian
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Shutong
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Enxin
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Li
authors.initials: L
authors.lastname: Bin
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Zong
authors.initials: Z
authors.lastname: Chuanlong
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Hua
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Si
authors.initials: S
authors.lastname: Yanhong
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China.
authors.forename: Du
authors.initials: D
authors.lastname: Yunsai
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong, Institute of Atherosclerosis, Taishan Medical University, Taian, China; Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease and Hebei Key Laboratory of Vascular Homeostasis, Shijiazhuang, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shucun
authors.affiliation: College of Animal Science and Technology, Shandong Agricultural University, Tai'an, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Hui
mesh_terms: D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects*; D004353:Drug Evaluation, Preclinical; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000502:physiology*; D008810:Mice, Inbred C57BL; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D054377:Chemokine CXCL12; D010455:Peptides; D014409:Tumor Necrosis Factor-alpha; C000607988:reverse-D-4F peptide; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt