title: Implication of transient receptor potential vanilloid type 1 in 14,15-epoxyeicosatrienoic acid-induced angiogenesis.
abstract: 14,15-epoxyeicosatrienoic acid (14,15-EET) is implicated in regulating physiological functions of endothelial cells (ECs), yet the potential molecular mechanisms underlying the beneficial effects in ECs are not fully understood. In this study, we investigated whether transient receptor potential vanilloid receptor type 1 (TRPV1) is involved in 14,15-EET-mediated Ca(2+) influx, nitric oxide (NO) production and angiogenesis. In human microvascular endothelial cells (HMECs), 14,15-EET time-dependently increased the intracellular level of Ca(2+). Removal of extracellular Ca(2+), pharmacological inhibition or genetic disruption of TRPV1 abrogated 14,15-EET-mediated increase of intracellular Ca(2+) level in HMECs or TRPV1-transfected HEK293 cells. Furthermore, removal of extracellular Ca(2+) or pharmacological inhibition of TRPV1 decreased 14,15-EET-induced NO production. 14,15-EET-mediated tube formation was abolished by TRPV1 pharmacological inhibition. In an animal experiment, 14,15-EET-induced angiogenesis was diminished by inhibition of TRPV1 and in TRPV1-deficient mice. TRPV1 may play a crucial role in 14,15-EET-induced Ca(2+) influx, NO production and angiogenesis.
authors.affiliation: 1. Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, 11221 Taiwan;
authors.forename: Kuo-Hui
authors.initials: KH
authors.lastname: Su
authors.affiliation: 1. Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, 11221 Taiwan;
authors.forename: Kuan-I
authors.initials: KI
authors.lastname: Lee
authors.affiliation: 2. Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529 Taiwan;
authors.forename: Song-Kun
authors.initials: SK
authors.lastname: Shyue
authors.affiliation: 1. Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, 11221 Taiwan;
authors.forename: Hsiang-Ying
authors.initials: HY
authors.lastname: Chen
authors.affiliation: 3. Heart Center, Cheng-Hsin General Hospital, Taipei, 11221 Taiwan.
authors.forename: Jeng
authors.initials: J
authors.lastname: Wei
authors.affiliation: 1. Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, 11221 Taiwan;
authors.forename: Tzong-Shyuan
authors.initials: TS
authors.lastname: Lee
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D042783:Endothelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009569:Nitric Oxide; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000235:genetics / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D014665:Vasodilator Agents; D009569:Nitric Oxide; C046782:14,15-epoxy-5,8,11-eicosatrienoic acid; D015126:8,11,14-Eicosatrienoic Acid; D002118:Calcium
keywords: angiogenesis; calcium; endothelial cell.; epoxyeicosatrienoic acid; transient receptor potential vanilloid 1