title: Urotensin II stimulates vascular endothelial growth factor secretion from adventitial fibroblasts in synergy with angiotensin II.
abstract: BACKGROUND
  The adventitia plays an important role in and is considered to be the initiating site for vascular remodeling. Urotensin II (UII) and angiotensin II (Ang II) are the two most important vascular peptides involved in vascular remodeling in the adventitia. Nevertheless, little is known about their effect on the expression of vascular endothelial growth factor (VEGF). It was hypothesized that both UII and Ang II could induce VEGF expression in adventitial fibroblasts and VEGF may play a role in cell proliferation and collagen I synthesis induced by UII or Ang II.
  
  
  RESULTS
  Growth-arrested adventitial fibroblasts were incubated in serum-free medium with UII and/or Ang II and inhibitors of the mitogen-activated protein kinase (MAPK) pathway or VEGF-neutralizing antibodies. The VEGF expression was evaluated using enzyme-linked immunosorbent assay (ELISA), while the proliferation and collagen I synthesis were detected using methyl thiazol tetrazolium (MTT) assay and ELISA. It was found that: (1) both UII and Ang II could stimulate VEGF expression in adventitial fibroblasts and they had a synergistic effect; (2) MAPK pathway inhibitors could inhibit VEGF secretion induced by UII and/or Ang II; and (3) VEGF-neutralizing antibodies could inhibit UII/Ang II-induced cell proliferation and collagen synthesis in adventitial fibroblasts.
  
  
  CONCLUSIONS
  Induction of VEGF expression may be a new mechanism involved in vascular remodeling for UII and Ang II.
authors.affiliation: Department of Cardiology, Peking University First Hospital, No. 1, XiShiKu Street, XiCheng District 100034, Peoples Republic of China.
authors.forename: Nana
authors.initials: N
authors.lastname: Song
authors.forename: Wenhui
authors.initials: W
authors.lastname: Ding
authors.forename: Songyun
authors.initials: S
authors.lastname: Chu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Xiao
authors.initials: X
authors.lastname: Dong
authors.forename: Beibing
authors.initials: B
authors.lastname: Di
authors.forename: Chaoshu
authors.initials: C
authors.lastname: Tang
mesh_terms: D000804:Angiotensin II / Q000819:agonists / Q000494:pharmacology*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000096:biosynthesis; D003238:Connective Tissue / Q000378:metabolism*; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D008297:Male; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014579:Urotensins / Q000819:agonists / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D024042:Collagen Type I; D047428:Protein Kinase Inhibitors; D014579:Urotensins; D042461:Vascular Endothelial Growth Factor A; D014662:Vasoconstrictor Agents; C467498:vascular endothelial growth factor A, rat; D000804:Angiotensin II; C029677:urotensin II