PMID- 12566125
OWN - NLM
STAT- MEDLINE
DCOM- 20030429
LR  - 20190513
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 57
IP  - 2
DP  - 2003 Feb
TI  - Cardiac overexpression of monocyte chemoattractant protein-1 in transgenic mice 
      mimics ischemic preconditioning through SAPK/JNK1/2 activation.
PG  - 523-34
AB  - OBJECTIVE AND METHODS: Although a beneficial association between innate immunity 
      and ischemic preconditioning has recently been proposed, the mechanisms 
      responsible for this link are poorly understood. To test the hypothesis that 
      pro-inflammatory cytokines have a beneficial role in the activation of the cell 
      survival pathway mediated by ischemic preconditioning, we have studied transgenic 
      mice with cardiac myocyte specific overexpression of murine monocyte 
      chemoattractant protein-1 (MCP-1). The resistance to ischemia was studied by 
      performing 45-min (with or without injection of the SAPK/JNKs inhibitor D-JNKI1) 
      and 3-day left coronary artery occlusions as well as 45-min left coronary artery 
      occlusion followed by 3 days of reperfusion. In addition, quantitative Western 
      blot analyses for TNF-alpha, and SAPK/JNK1/2, ERK1/2 and p38 activity were 
      performed. RESULTS: Infarct size, expressed in percent of either the risk area or 
      the left ventricle, was reduced in transgenic mice when compared with control 
      after both, 45-min (14.7+/-2.6% vs. 52.0+/-2.4%; P<0.05) and 45-min occlusion 
      followed by 3 days of reperfusion (23.2+/-1.8% vs. 30.0+/-1.8%; P<0.05) but it 
      was not significantly different for 3-day occlusion. Western blot analyses showed 
      significantly increased levels of TNF-alpha (1.8-fold) and 
      phosphorylated-SAPK/JNK1/2 (1.5-fold) in transgenic hearts. 
      Phosphorylated-ERK1/2, and phosphorylated-p38 levels were unchanged. 
      Immunohistochemistry revealed that in transgenic mice monocytes/macrophages, 
      lymphocytes, and fibroblasts are the source of TNF-alpha, whereas myocytes have 
      increased phosphorylated-SAPK/JNK1/2 levels. In addition, injection of the 
      SAPK/JNKs inhibitor D-JNKI1 partially abrogated the cardioprotective effect 
      observed in untreated transgenic mice. CONCLUSION: Overexpression of MCP-1 by 
      cardiomyocytes causes chronic infiltration and activation of leukocytes, 
      resulting in elevated TNF-alpha secretion and SAPK/JNK1/2 activation. The 
      activation of this pathway is in part responsible for the preconditioning effect 
      of MCP-1 overexpression. These results show a possible beneficial link between 
      innate immunity and ischemic preconditioning through MAP-kinase activation.
FAU - Martire, Alessandra
AU  - Martire A
AD  - Department of Experimental Cardiology, Max-Planck-Institute, Benekestrasse 2, 
      D-61231 Bad Nauheim, Germany. a.martire@kerckhoff.mpg.de
FAU - Fernandez, Borja
AU  - Fernandez B
FAU - Buehler, Alexandra
AU  - Buehler A
FAU - Strohm, Claudia
AU  - Strohm C
FAU - Schaper, Jutta
AU  - Schaper J
FAU - Zimmermann, Rene
AU  - Zimmermann R
FAU - Kolattukudy, Pappachan E
AU  - Kolattukudy PE
FAU - Schaper, Wolfgang
AU  - Schaper W
LA  - eng
PT  - Journal Article
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Chemokine CCL2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 8)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Blotting, Western
MH  - Chemokine CCL2/*metabolism
MH  - Heart Ventricles/immunology/metabolism/pathology
MH  - *Ischemic Preconditioning, Myocardial
MH  - Mice
MH  - Mice, Transgenic
MH  - Mitogen-Activated Protein Kinase 8
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Myocardial Infarction/*immunology/pathology
MH  - Myocytes, Cardiac/*immunology/metabolism
MH  - Phosphorylation
MH  - Signal Transduction/immunology
MH  - Tumor Necrosis Factor-alpha/metabolism
EDAT- 2003/02/05 04:00
MHDA- 2003/04/30 05:00
CRDT- 2003/02/05 04:00
PHST- 2003/02/05 04:00 [pubmed]
PHST- 2003/04/30 05:00 [medline]
PHST- 2003/02/05 04:00 [entrez]
AID - S0008636302006971 [pii]
AID - 10.1016/s0008-6363(02)00697-1 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2003 Feb;57(2):523-34. doi: 10.1016/s0008-6363(02)00697-1.