title: Resistance to neointimal hyperplasia and fatty streak formation in mice with adrenomedullin overexpression.
abstract: OBJECTIVE
  Several in vitro studies have implicated that adrenomedullin (AM) plays an important role in the pathogenesis of vascular injury and fatty streak formation. To test this possibility in vivo, we evaluated 2 experimental models using transgenic mice overexpressing AM in a vessel-selective manner (AMTg mice).
  
  
  RESULTS
  Placement of a periarterial cuff on femoral arteries resulted in neointimal formation at 2 to 4 weeks to a lesser extent in AMTg mice than in their wild-type littermates (at 28 days, intima/media area ratio 0.45+/-0.14 versus 1.31+/-0.41, respectively; P<0.001). This vasculoprotective effect observed in AMTg mice was inhibited by N(omega)-nitro-L-arginine methyl ester. We further examined the effect of AM on hypercholesterolemia-induced fatty streak formation by crossing AMTg mice with apolipoprotein E knockout mice (ApoEKO mice). The extent of the formation of fatty streak lesions was significantly less in ApoEKO/AMTg mice than in ApoEKO mice (percent lesion area 12.0+/-3.9% versus 15.8+/-2.8%, respectively; P<0.05). Moreover, endothelium-dependent vasodilatation as indicative of NO production was superior in AMTg/ApoEKO mice compared with ApoEKO mice.
  
  
  CONCLUSIONS
  Taken together, our data demonstrated that AM possesses a vasculoprotective effect in vivo, which is at least partially mediated by NO.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Imai
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shindo
authors.forename: Koji
authors.initials: K
authors.lastname: Maemura
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kurihara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Akishita
authors.forename: Junichi
authors.initials: J
authors.lastname: Osuga
authors.forename: Shun
authors.initials: S
authors.lastname: Ishibashi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Tobe
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morita
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Oh-hashi
authors.forename: Toru
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Maekawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Naoto
authors.initials: N
authors.lastname: Minamino
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Yazaki
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
authors.forename: Hiroki
authors.initials: H
authors.lastname: Kurihara
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D053607:Adrenomedullin; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D005263:Femoral Artery / Q000378:metabolism / Q000473:pathology; D006830:Hydralazine / Q000494:pharmacology; D006965:Hyperplasia / Q000517:prevention & control; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000378:metabolism*; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E; D010446:Peptide Fragments; D010455:Peptides; C058636:calcitonin gene-related peptide (8-37); D053607:Adrenomedullin; D006830:Hydralazine; D009569:Nitric Oxide; D015740:Calcitonin Gene-Related Peptide; D019331:NG-Nitroarginine Methyl Ester