PMID- 16251994
OWN - NLM
STAT- MEDLINE
DCOM- 20060522
LR  - 20121115
IS  - 0969-7128 (Print)
IS  - 0969-7128 (Linking)
VI  - 13
IP  - 4
DP  - 2006 Feb
TI  - Dominant-negative c-Jun inhibits rat cardiac hypertrophy induced by angiotensin 
      II and hypertension.
PG  - 348-55
AB  - Cardiac activator protein-1 (AP-1), composed of c-Jun, is significantly activated 
      by hypertension or angiotensin II (AngII). This study was undertaken to elucidate 
      whether c-Jun could be the potential target for treatment of cardiac hypertrophy. 
      We constructed recombinant adenovirus carrying dominant-negative mutant of c-Jun 
      (Ad.DN-c-Jun). Using catheter-based technique of adenoviral gene transfer, we 
      achieved global myocardial transduction of DN-c-Jun in rats, to specifically 
      inhibit cardiac AP-1. (1) AngII (200 ng/kg/min) infusion in rats caused cardiac 
      hypertrophy, increased cardiac p70S6 kinase activity by 1.3-fold (P<0.05) and 
      enhanced the gene expression of cardiac hypertrophic markers. Ad.DN-c-Jun, which 
      was transferred to the heart 2 days before AngII infusion, prevented cardiac 
      hypertrophy (P<0.01), decreased p70S6 kinase phosphorylation (P<0.05), and 
      suppressed cardiac gene expression of brain natriuretic peptide, collagen I, III, 
      and IV, monocyte chemoattractant protein-1 (MCP-1) and plasminogen activator 
      inhibitor-1 (PAI-1) (P<0.01). (2) In genetically hypertensive rats with cardiac 
      hypertrophy, cardiac gene transfer of Ad.DN-c-Jun, without affecting 
      hypertension, regressed cardiac hypertrophy (P<0.05), and suppressed p70S6 kinase 
      phosphorylation by 20% (P<0.05) and suppressed the enhanced expression of 
      collagen I, III, and IV, MCP-1 and PAI-1. These results provided the first 
      evidence that in vivo blockade of cardiac c-Jun inhibits pathologic cardiac 
      hypertrophy.
FAU - Kim-Mitsuyama, S
AU  - Kim-Mitsuyama S
AD  - Department of Pharmacology and Molecular Therapeutics, Kumamoto University 
      Graduate School of Medical Sciences, Kumamoto, Japan. 
      kimmitsu@gpo.kumamoto-u.ac.jp
FAU - Izumi, Y
AU  - Izumi Y
FAU - Izumiya, Y
AU  - Izumiya Y
FAU - Namba, M
AU  - Namba M
FAU - Yoshida, K
AU  - Yoshida K
FAU - Wake, R
AU  - Wake R
FAU - Yoshiyama, M
AU  - Yoshiyama M
FAU - Iwao, H
AU  - Iwao H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Gene Ther
JT  - Gene therapy
JID - 9421525
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Collagen Type I)
RN  - 0 (Collagen Type III)
RN  - 0 (Collagen Type IV)
RN  - 0 (Plasminogen Activator Inhibitor 1)
RN  - 0 (Transcription Factor AP-1)
RN  - 11128-99-7 (Angiotensin II)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
SB  - IM
MH  - Adenoviridae/genetics
MH  - Angiotensin II/adverse effects/metabolism
MH  - Animals
MH  - Blotting, Western/methods
MH  - Cardiomegaly/etiology/metabolism/*prevention & control
MH  - Chemokine CCL2/metabolism
MH  - Collagen Type I/metabolism
MH  - Collagen Type III/metabolism
MH  - Collagen Type IV/metabolism
MH  - *Gene Deletion
MH  - *Genes, Dominant
MH  - Genetic Therapy/*methods
MH  - Genetic Vectors/administration & dosage/genetics
MH  - Hypertension/complications/metabolism
MH  - Injections
MH  - Male
MH  - Models, Animal
MH  - Natriuretic Peptide, Brain/genetics
MH  - Phosphorylation
MH  - Plasminogen Activator Inhibitor 1/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Transcription Factor AP-1/*genetics/metabolism
EDAT- 2005/10/28 09:00
MHDA- 2006/05/23 09:00
CRDT- 2005/10/28 09:00
PHST- 2005/10/28 09:00 [pubmed]
PHST- 2006/05/23 09:00 [medline]
PHST- 2005/10/28 09:00 [entrez]
AID - 3302670 [pii]
AID - 10.1038/sj.gt.3302670 [doi]
PST - ppublish
SO  - Gene Ther. 2006 Feb;13(4):348-55. doi: 10.1038/sj.gt.3302670.