title: Apolipoprotein A-I mimetic peptide D-4F promotes human endothelial progenitor cell proliferation, migration, adhesion though eNOS/NO pathway.
abstract: Circulating endothelial progenitor cells (EPCs) have a critical role in endothelial maintenance and repair. Apolipoprotein A-I mimetic peptide D-4F has been shown to posses anti-atherogenic properties via sequestration of oxidized phospholipids, induction of remodeling of high density lipoprotein and promotion of cholesterol efflux from macrophage-derived foam cells. In this study, we test the effects of D-4F on EPC biology. EPCs were isolated from the peripheral venous blood of healthy male volunteers and characterized by 1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine-labeled acetylated LDL uptake and ulex europaeus agglutinin binding and flow cytometry. Cell proliferation, migration, adhesion, nitric oxide production and endothelial nitric oxide synthase (eNOS) expression in the absence and presence of D-4F or simvastatin (as a positive control), were assayed. We demonstrated that D-4F significantly enhanced EPC proliferation, migration and adhesion in a dose-dependent manner compared with vehicle. However, all of the favorable effects of D-4F on EPCs were dramatically attenuated by preincubation with NOS inhibitor L-NAME. Further, D-4F also increased nitric oxide production in culture supernatant and the levels of eNOS expression and phosphorylation. The stimulatory effects of D-4F (10 μg/ml) on EPC biology were comparable to 0.5 μM simvastatin. These results suggest that eNOS/NO pathway mediates the functional modulation of EPC biology in response to D-4F treatment and support the notion that the beneficial role of D-4F on EPCs may be one of the important components of its anti-atherogenic potential.
authors.affiliation: Department of Cardiology, The Second Clinic Medical College, Yangzhou University, Yangzhou, 225001, China.
authors.forename: Zhengang
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Qun
authors.forename: Chunmei
authors.initials: C
authors.lastname: Cao
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.forename: Lin
authors.initials: L
authors.lastname: Du
authors.forename: Pei
authors.initials: P
authors.lastname: Zhao
authors.forename: Kaizheng
authors.initials: K
authors.lastname: Gong
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology
chemical_list: D016632:Apolipoprotein A-I; C465468:D-4F peptide; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III