PMID- 16643875
OWN - NLM
STAT- MEDLINE
DCOM- 20070329
LR  - 20211020
IS  - 0008-6363 (Print)
IS  - 0008-6363 (Linking)
VI  - 71
IP  - 1
DP  - 2006 Jul 1
TI  - Monocyte-specific Bcl-2 expression attenuates inflammation and heart failure in 
      monocyte chemoattractant protein-1 (MCP-1)-induced cardiomyopathy.
PG  - 139-48
AB  - OBJECTIVE: Infiltrating inflammatory cells within the myocardium have been shown 
      to be apoptotic, but the significance of apoptotic inflammatory cells to the 
      development of cardiomyopathy remains undefined. Transgenic mice with 
      cardiac-specific expression of MCP-1 exhibit extensive apoptosis of infiltrating 
      mononuclear cells and develop heart failure. Here, we tested the hypothesis that 
      in vivo selective inhibition of apoptosis of infiltrating mononuclear cells would 
      preserve cardiac structure and function and improve survival in this murine 
      model. METHODS: Mice with cardiac-specific expression of MCP-1 and 
      monocyte-specific expression of Bcl-2 were generated by cross-breeding MCP-1 
      transgenic mice with hMRP8-Bcl-2 mice that over-express Bcl-2 in the monocytes. 
      Structural and functional parameters and the inflammatory response of the heart 
      were evaluated and compared between the wild-type and transgenic mice. RESULTS: 
      Expression of Bcl-2 in monocytes results in superior preservation of myocardial 
      structure, cardiac function and a significant prolongation of survival of MCP-1 
      transgenic mice. The beneficial effects of monocyte-specific Bcl-2 expression are 
      associated with inhibition of apoptosis of infiltrating mononuclear cells, 
      normalization of circulating C-reactive protein levels, attenuation of cellular 
      infiltrates, macrophage activation and production of proinflammatory cytokines, 
      tumor necrosis factor (TNF-alpha), interleukin (IL)-1 beta and IL-6 in the 
      hearts. CONCLUSIONS: These results demonstrate that apoptosis of infiltrating 
      mononuclear cells plays a detrimental role in the development of heart failure in 
      this murine model, suggesting that modulation of apoptosis of infiltrating 
      mononuclear cells may be of clinical benefit in heart failure.
FAU - Niu, Jianli
AU  - Niu J
AD  - Biomolecular Science Center and Department of Molecular Biology and Microbiology, 
      Burnett College of Biomedical Science, University of Central Florida, FL 32816, 
      USA. jniu@mail.ucf.edu
FAU - Azfer, Asim
AU  - Azfer A
FAU - Kolattukudy, Pappachan E
AU  - Kolattukudy PE
LA  - eng
GR  - R01 HL069458/HL/NHLBI NIH HHS/United States
GR  - R56 HL069458/HL/NHLBI NIH HHS/United States
GR  - HL-69458/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060316
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (Biomarkers)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Biomarkers/blood
MH  - C-Reactive Protein/analysis
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Chemotaxis, Leukocyte
MH  - Echocardiography
MH  - Gene Expression
MH  - Heart Failure/*immunology/metabolism
MH  - Immunohistochemistry/methods
MH  - In Situ Nick-End Labeling
MH  - Interleukin-1beta/blood
MH  - Interleukin-6/blood
MH  - Lymphocytes/*metabolism/pathology
MH  - Macrophage Activation
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Mice, Transgenic
MH  - Myocardium/*metabolism/pathology
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Survival Analysis
MH  - Tumor Necrosis Factor-alpha/blood
PMC - PMC1523424
MID - NIHMS11270
EDAT- 2006/04/29 09:00
MHDA- 2007/03/30 09:00
PMCR- 2008/01/28
CRDT- 2006/04/29 09:00
PHST- 2005/11/30 00:00 [received]
PHST- 2006/03/06 00:00 [revised]
PHST- 2006/03/08 00:00 [accepted]
PHST- 2006/04/29 09:00 [pubmed]
PHST- 2007/03/30 09:00 [medline]
PHST- 2006/04/29 09:00 [entrez]
PHST- 2008/01/28 00:00 [pmc-release]
AID - S0008-6363(06)00122-2 [pii]
AID - 10.1016/j.cardiores.2006.03.008 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2006 Jul 1;71(1):139-48. doi: 10.1016/j.cardiores.2006.03.008. 
      Epub 2006 Mar 16.