title: The effects of DPP-4 inhibitor on hypoxia-induced apoptosis in human umbilical vein endothelial cells.
abstract: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral hypoglycemic agents for patients with type 2 diabetes mellitus and have potential antiatherosclerotic properties. Meanwhile, it is unclear how DPP-4 inhibitors have protective effects on atherosclerosis. Our aim was to determine the effects and its mechanisms of DPP-4 inhibitors on cultured endothelial cells. Human umbilical vein endothelial cells (HUVECs) were cultured in hypoxic condition. To evaluate the protective effects of DPP-4 inhibitor on HUVECs, DPP-4 inhibitor was added in the cell culture medium and the cell viability was assessed by TUNEL assay. And we examined the intracellular signaling pathways in relation to the effects of DPP-4 inhibitor. DPP-4 inhibition had beneficial effects by inhibiting the apoptosis under hypoxic conditions in HUVECs. The antiapoptotic effects of DPP-4 inhibitor were abolished by the pretreatment with a CXCR4 antagonist or a Stat3 inhibitor. DPP-4 inhibition has beneficial effects on HUVECs by inhibiting the apoptosis under hypoxic conditions. SDF-1α/CXCR4/Stat3 pathways might be involved in the mechanisms of the cytoprotective effects of DPP-4 inhibitor. These results suggested that DPP-4 inhibitor has a potential for protecting vessels.
authors.affiliation: Department of Molecular Cardiovascular Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Nagamine
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hasegawa
authors.affiliation: Department of Molecular Cardiovascular Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Hashimoto
authors.affiliation: Department of Molecular Cardiovascular Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Yamada-Inagawa
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hirose
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kobara
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tadokoro
authors.affiliation: Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kobayashi
authors.affiliation: Department of Molecular Cardiovascular Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan. Electronic address: htakano-cib@umin.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takano
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054377:Chemokine CXCL12 / Q000096:biosynthesis; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis* / Q000378:metabolism; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D009842:Oligopeptides / Q000494:pharmacology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054873:Dipeptidyl-Peptidase IV Inhibitors; D009842:Oligopeptides; D019718:Receptors, CXCR4; D050796:STAT3 Transcription Factor; C041445:diprotin A; C042807:DPP4 protein, human; D018819:Dipeptidyl Peptidase 4
keywords: Apoptosis; Dipeptidyl peptidase-4; Endothelial cell; Hypoxia