title: Lack of JunD promotes pressure overload-induced apoptosis, hypertrophic growth, and angiogenesis in the heart.
abstract: BACKGROUND
  The Jun family of activator protein 1 (AP-1) transcription factors (c-Jun, JunB, and JunD) is involved in fundamental biological processes such as proliferation, apoptosis, tumor angiogenesis, and hypertrophy. The role of individual AP-1 transcription factors in the stressed heart is not clear. In the present study we analyzed the role of JunD in survival, hypertrophy, and angiogenesis in the pressure-overloaded mouse heart after thoracic aortic constriction.
  
  
  RESULTS
  Mice lacking JunD (knockout [KO]) showed increased mortality and enhanced cardiomyocyte apoptosis and fibrosis associated with increased levels of hypoxia-induced factor-1alpha, vascular endothelial growth factor (VEGF), p53, and Bax protein and reduced levels of Bcl-2 protein after 7 days of severe pressure overload compared with wild-type (WT) siblings. Cardiomyocyte hypertrophy in surviving KO mice was enhanced compared with that in WT mice. Chronic moderate pressure overload for 12 weeks caused enhanced left ventricular hypertrophy in KO mice, and survival and interstitial fibrosis were comparable with WT mice. Cardiac function, 12 weeks after operation, was comparable among shams and pressure-overloaded mice of both genotypes. In addition, KO mice exposed to chronic pressure overload showed higher cardiac capillary density associated with increased protein levels of VEGF.
  
  
  CONCLUSIONS
  Thus, JunD limits cardiomyocyte hypertrophy and protects the pressure-overloaded heart from cardiac apoptosis. These beneficial effects of JunD, however, are associated with antiangiogenic properties.
authors.affiliation: Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany. hilfiker.denise@mh-hannover.de
authors.forename: Denise
authors.initials: D
authors.lastname: Hilfiker-Kleiner
authors.forename: Andres
authors.initials: A
authors.lastname: Hilfiker
authors.forename: Karol
authors.initials: K
authors.lastname: Kaminski
authors.forename: Arnd
authors.initials: A
authors.lastname: Schaefer
authors.forename: Joon-Keun
authors.initials: JK
authors.lastname: Park
authors.forename: Kim
authors.initials: K
authors.lastname: Michel
authors.forename: Anja
authors.initials: A
authors.lastname: Quint
authors.forename: Moshe
authors.initials: M
authors.lastname: Yaniv
authors.forename: Jonathan B
authors.initials: JB
authors.lastname: Weitzman
authors.forename: Helmut
authors.initials: H
authors.lastname: Drexler
mesh_terms: D000328:Adult; D000818:Animals; D017209:Apoptosis; D002196:Capillaries / Q000502:physiology; D006332:Cardiomegaly / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology*; D002311:Cardiomyopathy, Dilated / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007763:Lac Operon; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology*; D010641:Phenotype; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D017725:Ventricular Pressure
chemical_list: D016755:Proto-Oncogene Proteins c-jun; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A