PMID- 16627625
OWN - NLM
STAT- MEDLINE
DCOM- 20060719
LR  - 20220227
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 20
IP  - 8
DP  - 2006 Jun
TI  - Inhibition of protein phosphatase 1 by inhibitor-2 gene delivery ameliorates 
      heart failure progression in genetic cardiomyopathy.
PG  - 1197-9
AB  - The type 1 protein phosphatase (PP1) has been reported to be overactivated in the 
      failing heart, leading to a depression in cardiac function. We investigated 
      whether in vivo PP1 inhibition by myocardial gene transfer of inhibitor-2 
      (INH-2), an endogenous PP1 inhibitor, alleviates heart failure (HF) progression 
      in the cardiomyopathic (CM) hamster, a well-established HF model. Adenoviral 
      INH-2 gene delivery improved % fractional shortening of the left ventricle (LV) 
      accompanied by reduced chamber size at 1 wk. In vivo myocardial INH-2 gene 
      delivery induced an increase in cytosolic PP1 catalytic subunit alpha (PP1Calpha) 
      without inducing the corresponding increase in cytosolic PP1 activity. On the 
      other hand, INH-2 delivery induced a decrease in microsomal PP1Calpha, resulting 
      in a preferential decrease in microsomal PP1 activity, thereby increasing in 
      phospholamban phosphorylation at Ser16. INH-2 gene transfer alleviated brain 
      natriuretic peptide expression, presumably reflecting improved cardiac function. 
      Moreover, adeno-associated virus-mediated INH-2 gene delivery significantly 
      extended the survival time for 3 mo. These results indicate that increased PP1 
      activity is an exacerbating factor during progression of genetic cardiomyopathy 
      and modulation of PP1 activity by INH-2 provides a potential new treatment for HF 
      without activating protein kinase A signaling in cardiomyocytes.
FAU - Yamada, Michio
AU  - Yamada M
AD  - Department of Molecular Cardiovascular Biology, Yamaguchi University School of 
      Medicine, 1-1-1 Minami-Kogushi, Ube 755-8505, Japan.
FAU - Ikeda, Yasuhiro
AU  - Ikeda Y
FAU - Yano, Masafumi
AU  - Yano M
FAU - Yoshimura, Koichi
AU  - Yoshimura K
FAU - Nishino, Shizuka
AU  - Nishino S
FAU - Aoyama, Hidekazu
AU  - Aoyama H
FAU - Wang, Lili
AU  - Wang L
FAU - Aoki, Hiroki
AU  - Aoki H
FAU - Matsuzaki, Masunori
AU  - Matsuzaki M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060420
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Proteins)
RN  - 0 (protein phosphatase inhibitor-2)
RN  - EC 3.1.3.16 (Phosphoprotein Phosphatases)
RN  - EC 3.1.3.16 (Protein Phosphatase 1)
SB  - IM
MH  - Animals
MH  - Cardiac Output, Low/physiopathology/*therapy
MH  - Cardiomyopathy, Dilated/genetics/*therapy
MH  - Cricetinae
MH  - Dependovirus/genetics
MH  - Disease Progression
MH  - Genetic Vectors
MH  - Male
MH  - Myocardium/*enzymology
MH  - Myocytes, Cardiac/enzymology
MH  - Phosphoprotein Phosphatases/*antagonists & inhibitors
MH  - Protein Phosphatase 1
MH  - Proteins/*genetics
MH  - Rats
MH  - Rats, Wistar
MH  - Survival Analysis
MH  - Transduction, Genetic
MH  - Ventricular Function, Left
EDAT- 2006/04/22 09:00
MHDA- 2006/07/20 09:00
CRDT- 2006/04/22 09:00
PHST- 2006/04/22 09:00 [pubmed]
PHST- 2006/07/20 09:00 [medline]
PHST- 2006/04/22 09:00 [entrez]
AID - fj.05-5299fje [pii]
AID - 10.1096/fj.05-5299fje [doi]
PST - ppublish
SO  - FASEB J. 2006 Jun;20(8):1197-9. doi: 10.1096/fj.05-5299fje. Epub 2006 Apr 20.