title: The apolipoprotein A-I mimetic peptide, D-4F, alleviates ox-LDL-induced oxidative stress and promotes endothelial repair through the eNOS/HO-1 pathway.
abstract: Apolipoprotein A-I (apoA-I) mimetic peptide exerts many anti-atherogenic properties. However, the underlying mechanisms related to the endothelial protective effects remain elusive. In this study, the apoA-I mimetic peptide, D-4F, was used. Proliferation assay, wound healing, and transwell migration experiments showed that D-4F improved the impaired endothelial proliferation and migration resulting from ox-LDL. Endothelial adhesion molecules expression and monocyte adhesion assay demonstrated that D-4F inhibited endothelial inflammation. Caspase-3 activation and TUNEL stain indicated that D-4F reduced endothelial cell apoptosis. A pivotal anti-oxidant enzyme, heme oxygenase-1 (HO-1) was upregulated by D-4F. The Akt/AMPK/eNOS pathways were involved in the expression of HO-1 induced by D-4F. Moreover, the anti-oxidation, pro-proliferation, and pro-migration capacities of D-4F were diminished by the inhibitors of both eNOS (L-NAME) and HO-1 (Znpp). Additionally, downregulation of ATP-binding cassette transporter A1 (ABCA1) by siRNA abolished the activation of Akt, AMPK and eNOS, and reduced the upregulation of HO-1 triggered by D-4F. Furthermore, D-4F promoted the reendothelialization of injured intima in carotid artery injury model of C57BL/6J mice in vivo. In summary, these findings suggested that D-4F might be a powerful candidate in the protection of endothelial cells and the prevention of cardiovascular disease (CVD).
authors.affiliation: Department of Cardiology, the Affiliated Xiamen Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen 361004, China. Electronic address: liudh@xmu.edu.cn.
authors.forename: Donghui
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Cardiology, the Affiliated Xiamen Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen 361004, China; Union Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Department of Cardiology, the Affiliated Xiamen Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen 361004, China; Union Clinical Medical College of Fujian Medical University, Fuzhou 350001, China.
authors.forename: Mengzhang
authors.initials: M
authors.lastname: Wu
authors.affiliation: High-field NMR Research Center, MOE Key Laboratory of Spectrochemical Analysis& Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
authors.forename: Wenqi
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Cardiology, the Affiliated Xiamen Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen 361004, China.
authors.forename: Mingming
authors.initials: M
authors.lastname: Qian
authors.affiliation: Department of Cardiology, the Affiliated Xiamen Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen 361004, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of Cardiology, the Affiliated Xiamen Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen 361004, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Ob/Gyn and Neonatal and Reproductive Medicine, the People's Liberation Army 174th Hospital and the Affiliated Hospital of Xiamen University, Xiamen 361003, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Ob/Gyn and Neonatal and Reproductive Medicine, the People's Liberation Army 174th Hospital and the Affiliated Hospital of Xiamen University, Xiamen 361003, China.
authors.forename: Jianlan
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Cardiology, the Affiliated Xiamen Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen 361004, China.
authors.forename: He
authors.initials: H
authors.lastname: Chang
authors.affiliation: Department of Physical Education, Xiamen University of Technology, Xiamen 361021, China.
authors.forename: Caihua
authors.initials: C
authors.lastname: Huang
authors.affiliation: High-field NMR Research Center, MOE Key Laboratory of Spectrochemical Analysis& Instrumentation, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, China.
authors.forename: Donghai
authors.initials: D
authors.lastname: Lin
authors.affiliation: Department of Cardiology, the Affiliated Xiamen Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen 361004, China. Electronic address: wy@medmail.com.cn.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D002448:Cell Adhesion; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008297:Male; D051379:Mice; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012038:Regeneration; D015398:Signal Transduction / Q000187:drug effects*; D014945:Wound Healing
chemical_list: D016632:Apolipoprotein A-I; C465468:D-4F peptide; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D052250:Nitric Oxide Synthase Type III; D051547:Heme Oxygenase-1; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases
keywords: Endothelial cell; HO-1; Migration; Proliferation; apoA-I mimetic peptide