PMID- 21666115
OWN - NLM
STAT- MEDLINE
DCOM- 20111101
LR  - 20220310
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 301
IP  - 3
DP  - 2011 Sep
TI  - Adiponectin mediates cardioprotection in oxidative stress-induced cardiac myocyte 
      remodeling.
PG  - H984-93
LID - 10.1152/ajpheart.00428.2011 [doi]
AB  - Reactive oxygen species (ROS) induce matrix metalloproteinase (MMP) activity that 
      mediates hypertrophy and cardiac remodeling. Adiponectin (APN), an adipokine, 
      modulates cardiac hypertrophy, but it is unknown if APN inhibits ROS-induced 
      cardiomyocyte remodeling. We tested the hypothesis that APN ameliorates 
      ROS-induced cardiomyocyte remodeling and investigated the mechanisms involved. 
      Cultured adult rat ventricular myocytes (ARVM) were pretreated with recombinant 
      APN (30 mug/ml, 18 h) followed by exposure to physiologic concentrations of 
      H(2)O(2) (1-200 muM). ARVM hypertrophy was measured by [(3)H]leucine incorporation 
      and atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP) gene 
      expression by RT-PCR. MMP activity was assessed by in-gel zymography. ROS was 
      induced with angiotensin (ANG)-II (3.2 mg.kg(-1).day(-1) for 14 days) in 
      wild-type (WT) and APN-deficient (APN-KO) mice. Myocardial MMPs, tissue 
      inhibitors of MMPs (TIMPs), p-AMPK, and p-ERK protein expression were determined. 
      APN significantly decreased H(2)O(2)-induced cardiomyocyte hypertrophy by 
      decreasing total protein, protein synthesis, ANF, and BNP expression. 
      H(2)O(2)-induced MMP-9 and MMP-2 activities were also significantly diminished by 
      APN. APN significantly increased p-AMPK in both nonstimulated and 
      H(2)O(2)-treated ARVM. H(2)O(2)-induced p-ERK activity and NF-kappaB activity were 
      both abrogated by APN pretreatment. ANG II significantly decreased myocardial 
      p-AMPK and increased p-ERK expression in vivo in APN-KO vs. WT mice. ANG II 
      infusion enhanced cardiac fibrosis and MMP-2-to-TIMP-2 and MMP-9-to-TIMP-1 ratios 
      in APN-KO vs. WT mice. Thus APN inhibits ROS-induced cardiomyocyte remodeling by 
      activating AMPK and inhibiting ERK signaling and NF-kappaB activity. Its effects on 
      ROS and ultimately on MMP expression define the protective role of APN against 
      ROS-induced cardiac remodeling.
FAU - Essick, Eric E
AU  - Essick EE
AD  - Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, 
      Massachusetts 02118, USA.
FAU - Ouchi, Noriyuki
AU  - Ouchi N
FAU - Wilson, Richard M
AU  - Wilson RM
FAU - Ohashi, Koji
AU  - Ohashi K
FAU - Ghobrial, Joanna
AU  - Ghobrial J
FAU - Shibata, Rei
AU  - Shibata R
FAU - Pimentel, David R
AU  - Pimentel DR
FAU - Sam, Flora
AU  - Sam F
LA  - eng
GR  - HL-079099/HL/NHLBI NIH HHS/United States
GR  - HL-095891/HL/NHLBI NIH HHS/United States
GR  - HL-102631/HL/NHLBI NIH HHS/United States
GR  - T32-HL-007224/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20110610
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Adiponectin)
RN  - 0 (Adipoq protein, mouse)
RN  - 0 (NF-kappa B)
RN  - 0 (Oxidants)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Recombinant Proteins)
RN  - 11128-99-7 (Angiotensin II)
RN  - 114471-18-0 (Natriuretic Peptide, Brain)
RN  - 85637-73-6 (Atrial Natriuretic Factor)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Adiponectin/deficiency/genetics/metabolism
MH  - Analysis of Variance
MH  - Angiotensin II
MH  - Animals
MH  - Atrial Natriuretic Factor/genetics/metabolism
MH  - Cardiomegaly/chemically induced/genetics/metabolism/pathology/*prevention & 
      control
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Fibrosis
MH  - Genes, Reporter
MH  - Hydrogen Peroxide/pharmacology
MH  - Hypertrophy, Left Ventricular/chemically 
      induced/genetics/metabolism/pathology/*prevention & control
MH  - Male
MH  - Matrix Metalloproteinases/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Myocytes, Cardiac/drug effects/*metabolism/pathology
MH  - NADPH Oxidases/metabolism
MH  - NF-kappa B/genetics/metabolism
MH  - Natriuretic Peptide, Brain/genetics/metabolism
MH  - Oxidants/pharmacology
MH  - *Oxidative Stress/drug effects
MH  - Phosphorylation
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Reactive Oxygen Species/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Signal Transduction
MH  - Time Factors
MH  - Transfection
MH  - *Ventricular Remodeling/drug effects
PMC - PMC3191107
EDAT- 2011/06/15 06:00
MHDA- 2011/11/02 06:00
PMCR- 2012/09/01
CRDT- 2011/06/14 06:00
PHST- 2011/06/14 06:00 [entrez]
PHST- 2011/06/15 06:00 [pubmed]
PHST- 2011/11/02 06:00 [medline]
PHST- 2012/09/01 00:00 [pmc-release]
AID - ajpheart.00428.2011 [pii]
AID - H-00428-2011 [pii]
AID - 10.1152/ajpheart.00428.2011 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2011 Sep;301(3):H984-93. doi: 
      10.1152/ajpheart.00428.2011. Epub 2011 Jun 10.