title: Moderate pulmonary arterial hypertension in male mice lacking the vasoactive intestinal peptide gene.
abstract: BACKGROUND
  Vasoactive intestinal peptide (VIP), a pulmonary vasodilator and inhibitor of vascular smooth muscle proliferation, has been reported absent in pulmonary arteries from patients with idiopathic pulmonary arterial hypertension (PAH). We have tested the hypothesis that targeted deletion of the VIP gene may lead to PAH with pulmonary vascular remodeling.
  
  
  RESULTS
  We examined VIP knockout (VIP-/-) mice for evidence of PAH, right ventricular (RV) hypertrophy, and pulmonary vascular remodeling. Relative to wild-type control mice, VIP-/- mice showed moderate RV hypertension, RV hypertrophy confirmed by increased ratio of RV to left ventricle plus septum weight, and enlarged, thickened pulmonary artery and smaller branches with increased muscularization and narrowed lumen. Lung sections also showed perivascular inflammatory cell infiltrates. No systemic hypertension and no arterial hypoxemia existed to explain the PAH. The condition was associated with increased mortality. Both the vascular remodeling and RV remodeling were attenuated after a 4-week treatment with VIP.
  
  
  CONCLUSIONS
  Deletion of the VIP gene leads to spontaneous expression of moderately severe PAH in mice during air breathing. Although not an exact model of idiopathic PAH, the VIP-/- mouse should be useful for studying molecular mechanisms of PAH and evaluating potential therapeutic agents. VIP replacement therapy holds promise for the treatment of PAH, and mutations of the VIP gene may be a factor in the pathogenesis of idiopathic PAH.
authors.affiliation: Departments of Medicine, State University of New York at Stony Brook, Stony Brook, NY, USA. sami.i.said@stonybrook.edu
authors.forename: Sami I
authors.initials: SI
authors.lastname: Said
authors.forename: Sayyed A
authors.initials: SA
authors.lastname: Hamidi
authors.forename: Kathleen G
authors.initials: KG
authors.lastname: Dickman
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Szema
authors.forename: Sergey
authors.initials: S
authors.lastname: Lyubsky
authors.forename: Richard Z
authors.initials: RZ
authors.lastname: Lin
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Jiang
authors.forename: John J
authors.initials: JJ
authors.lastname: Chen
authors.forename: James A
authors.initials: JA
authors.lastname: Waschek
authors.forename: Smadar
authors.initials: S
authors.lastname: Kort
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D018390:Gene Targeting; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D008168:Lung / Q000098:blood supply / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011651:Pulmonary Artery / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology*; D015996:Survival Rate; D014463:Ultrasonography; D014660:Vasoactive Intestinal Peptide / Q000172:deficiency* / Q000235:genetics* / Q000627:therapeutic use; D020257:Ventricular Remodeling / Q000187:drug effects / Q000235:genetics
chemical_list: D014660:Vasoactive Intestinal Peptide