title: Vascular endothelial cell-derived endothelin-1 mediates vascular inflammation and neointima formation following blood flow cessation.
abstract: OBJECTIVE
  Although endothelin-1 (ET-1) has been suggested to contribute to the pathogenesis of neointima formation and atherosclerosis, the individual roles of ET-1 derived from certain cell types in this disease remain unclear. In this study, we determined the role of vascular endothelial ET-1 on vascular inflammation and neointima formation using vascular endothelial ET-1-knockout [ET-1(f/f); Tie2-Cre (+)] mice.
  
  
  RESULTS
  Intimal hyperplasia was induced by complete ligation of the left carotid artery in 12-week-old male ET-1(f/f);Tie2-Cre (+) mice (n = 35) and the wild-type (WT) littermates (n = 34). Following this intervention, neointima formation was reduced in ET-1(f/f);Tie2-Cre (+) mice compared with the WT mice, independent of the difference in blood pressure. This reduction was associated with a decrease in inflammatory cell recruitment to the vessel wall, which was accompanied by reduced expression levels of endothelial adhesion molecules as well as chemokines and a decrease in vascular smooth muscle cell proliferation.
  
  
  CONCLUSIONS
  The results of our study provide direct evidence for the role of vascular endothelial ET-1 in mediating vascular inflammation and neointima formation following vascular injury in addition to promoting vasoconstriction and cell proliferation. Furthermore, this study suggests a strategy for the efficient design of ET receptor antagonists with targeted inhibition of ET-1 signalling in vascular endothelial cells.
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, 7-5-1 Kusunoki, Chuo, Kobe 650-0017, Japan.
authors.forename: Dyah W
authors.initials: DW
authors.lastname: Anggrahini
authors.forename: Noriaki
authors.initials: N
authors.lastname: Emoto
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakayama
authors.forename: Bambang
authors.initials: B
authors.lastname: Widyantoro
authors.forename: Suko
authors.initials: S
authors.lastname: Adiarto
authors.forename: Naoko
authors.initials: N
authors.lastname: Iwasa
authors.forename: Hidemi
authors.initials: H
authors.lastname: Nonaka
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Rikitake
authors.forename: Yaz Y
authors.initials: YY
authors.lastname: Kisanuki
authors.forename: Masashi
authors.initials: M
authors.lastname: Yanagisawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirata
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002339:Carotid Arteries / Q000601:surgery; D020212:Carotid Artery Injuries / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D049109:Cell Proliferation; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D019332:Endothelin-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006339:Heart Rate; D006965:Hyperplasia; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology; D019426:Integrases / Q000235:genetics; D008026:Ligation; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D042787:Receptor, TIE-2 / Q000235:genetics; D017466:Receptors, Endothelin / Q000378:metabolism; D012039:Regional Blood Flow; D013997:Time Factors; D017539:Tunica Intima / Q000378:metabolism* / Q000473:pathology
chemical_list: D015815:Cell Adhesion Molecules; D019332:Endothelin-1; D017466:Receptors, Endothelin; D042787:Receptor, TIE-2; C045073:Cre recombinase; D019426:Integrases