PMID- 22470108
OWN - NLM
STAT- MEDLINE
DCOM- 20120807
LR  - 20211217
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Linking)
VI  - 5
IP  - 6
DP  - 2012 Jun
TI  - Involvement of reactive oxygen species and JNK in increased expression of MCP-1 
      and infiltration of inflammatory cells in pressure-overloaded rat hearts.
PG  - 1491-6
LID - 10.3892/mmr.2012.852 [doi]
AB  - Increasing evidence has shown that inflammation is involved in pressure 
      overload-induced cardiac remodeling. Monocyte chemoattractant protein-1 (MCP-1) 
      plays a pivotal role in the inflammatory process. However, the mechanisms 
      underlying the upregulation of MCP-1 expression remain poorly understood. In the 
      present study, we examined the hypothesis that an increased production of 
      reactive oxygen species (ROS) mediates the upregulation of MCP-1. In a 
      pressure-overloaded rat heart model with abdominal aortic coarctation (AC), 
      superoxide dismutase-inhibitable cytochrome C reduction assay showed that ROS 
      generation in the myocardium increased significantly at 1 week by 61% (n=8, 
      P<0.01), peaked at 2 weeks and maintained these high levels for 4 weeks. The 
      elevation of ROS was paralleled by the increased expression of MCP-1 and left 
      ventricular remodeling (cardiac hypertrophy, perivascular and interstitial 
      fibrosis). The oral administration of the antioxidant, N-acetylcysteine (NAC, 0.2 
      g/kg/day), for 2 or 4 weeks, significantly attenuated ROS production by 69 and 
      68%, respectively (n=8, P<0.01), as well as left ventricular remodeling. NAC 
      treatment for 2 weeks also significantly reduced the MCP-1 mRNA and protein 
      levels by 52 and 60%, respectively (n=4-8, both P<0.01), but had no effect on 
      blood pressure. In the rats with AC at 2 weeks, when MCP-1 expression and 
      inflammation changes were overt, immunoblotting with phospho-specific antibodies 
      revealed that extracellular regulated kinase (ERK) and c-jun NH2-terminal kinase 
      (JNK), but not p38 mitogen-activated protein kinase, were activated. NAC 
      administration attenuated JNK activation, but had no effect on ERK. Our results 
      suggest that increased ROS production may play an important role in the increased 
      expression of MCP-1 in pressure overload-induced cardiac remodeling. JNK is 
      likely involved in the signaling pathway.
FAU - Shang, Fujun
AU  - Shang F
AD  - Department of Cardiology, Tangdu Hospital, The Fourth Military Medical 
      University, Xi'an, People's Republic of China.
FAU - Wang, Jiepin
AU  - Wang J
FAU - Liu, Xiongtao
AU  - Liu X
FAU - Li, Jun
AU  - Li J
FAU - Zheng, Qiangsun
AU  - Zheng Q
FAU - Xue, Yusheng
AU  - Xue Y
FAU - Zhao, Lianyou
AU  - Zhao L
LA  - eng
PT  - Journal Article
DEP - 20120330
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Antibodies, Phospho-Specific)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Administration, Oral
MH  - Animals
MH  - Antibodies, Phospho-Specific/immunology
MH  - Aortic Coarctation/physiopathology
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Free Radical Scavengers/pharmacology
MH  - Gene Expression Regulation
MH  - Heart/*physiopathology
MH  - JNK Mitogen-Activated Protein Kinases/*metabolism
MH  - Male
MH  - Myocardium/*metabolism
MH  - Pressure
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Reactive Oxygen Species/*metabolism
MH  - Signal Transduction/drug effects
MH  - Ventricular Remodeling/drug effects
OTO - NOTNLM
OT  - reactive oxygen species
OT  - hypertension
OT  - pressure overload-induced cardiac remodeling
OT  - monocyte chemoattractant protein-1
EDAT- 2012/04/04 06:00
MHDA- 2012/08/08 06:00
CRDT- 2012/04/04 06:00
PHST- 2011/12/02 00:00 [received]
PHST- 2012/03/22 00:00 [accepted]
PHST- 2012/04/04 06:00 [entrez]
PHST- 2012/04/04 06:00 [pubmed]
PHST- 2012/08/08 06:00 [medline]
AID - 10.3892/mmr.2012.852 [doi]
PST - ppublish
SO  - Mol Med Rep. 2012 Jun;5(6):1491-6. doi: 10.3892/mmr.2012.852. Epub 2012 Mar 30.