title: Activation of ERK pathway is required for 15-HETE-induced angiogenesis in human umbilical vascular endothelial cells.
abstract: Angiogenesis plays a critical role in the progression of cardiovascular disease, retinal ischemia, or tumorigenesis. The imbalance of endothelial cell proliferation and apoptosis disturbs the establishment of the vasculogenesis, which is affected by several arachidonic acid metabolites. 15-Hydroxyeicosatetraenoic acid (15-HETE) is one of the metabolites. However, the underlying mechanisms of angiogenesis induced by 15-HETE in human umbilical vascular endothelial cells (HUVECs) are still poorly understood. Since extracellular signal-regulated kinase (ERK) is a critical regulator of cell proliferation, there may be a crosstalk between 15-HETE-regulating angiogenic process and ERK-proliferative effect in HUVECs. To test this hypothesis, we study the effect of 15-HETE on cell proliferation, angiogenesis, and apoptosis using cell viability measurement, cell cycle analysis, western blot, scratch-wound, tube formation assay, and nuclear morphology determination. We found that 15-HETE promoted HUVEC angiogenesis, which were mediated by ERK. Moreover, 15-HETE-induced proliferation and cell cycle transition from the G(0)/G(1) phase to the G(2)/M + S phase. All these effects were reversed after blocking ERK with PD98059 (an ERK inhibitor). In addition, HUVEC apoptosis was relieved by 15-HETE through the ERK pathway. Thus, ERK is necessary for the effects of 15-HETE in the regulation of HUVEC angiogenesis, which may be a novel potential target for the treatment of angiogenesis-related diseases.
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University , Nangang District , Harbin, Heilongjiang , People's Republic of China .
authors.forename: Shuang
authors.initials: S
authors.lastname: Wang
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University , Nangang District , Harbin, Heilongjiang , People's Republic of China .
authors.forename: Weiwei
authors.initials: W
authors.lastname: Cao
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University , Nangang District , Harbin, Heilongjiang , People's Republic of China .
authors.forename: Hao
authors.initials: H
authors.lastname: Xing
authors.affiliation: b Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University - Daqing , Daqing, Heilongjiang Province , People's Republic of China , and.
authors.forename: Ying Li
authors.initials: YL
authors.lastname: Chen
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University , Nangang District , Harbin, Heilongjiang , People's Republic of China .
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University , Nangang District , Harbin, Heilongjiang , People's Republic of China .
authors.forename: Tingting
authors.initials: T
authors.lastname: Shen
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University , Nangang District , Harbin, Heilongjiang , People's Republic of China .|c Department of Biology , Georgia State University , Atlanta , GA , USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Jiang
authors.affiliation: a Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University , Nangang District , Harbin, Heilongjiang , People's Republic of China .|b Department of Biopharmaceutical Sciences , College of Pharmacy, Harbin Medical University - Daqing , Daqing, Heilongjiang Province , People's Republic of China , and.
authors.forename: Daling
authors.initials: D
authors.lastname: Zhu
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019925:Cyclin A / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects
chemical_list: D019925:Cyclin A; D006893:Hydroxyeicosatetraenoic Acids; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: 15-HETE; ERK; angiogenesis; apoptosis; human umbilical vascular endothelial cells; proliferation