PMID- 16678847
OWN - NLM
STAT- MEDLINE
DCOM- 20060829
LR  - 20211020
IS  - 0022-2828 (Print)
IS  - 1095-8584 (Electronic)
IS  - 0022-2828 (Linking)
VI  - 40
IP  - 6
DP  - 2006 Jun
TI  - Targeted cardiac expression of soluble Fas prevents the development of heart 
      failure in mice with cardiac-specific expression of MCP-1.
PG  - 810-20
AB  - Monocyte chemoattractant protein-1 (MCP-1) plays a crucial role in initiating 
      coronary heart disease by recruiting monocytes/macrophages to the vessel wall. 
      Transgenic mice with cardiac-specific expression of MCP-1 manifest cardiac 
      inflammation and develop heart failure. The pathways mediating the detrimental 
      effects of MCP-1 expression have not been defined. We postulate that the Fas 
      ligand (FasL) derived from the infiltrating mononuclear cells causes death of 
      cardiac cells resulting in the development of heart failure. Here, we tested this 
      hypothesis by determining whether inhibition of FasL function through 
      cardiac-specific expression of soluble Fas (sFas) would rescue the MCP-1 
      transgenic mice from developing heart failure. We generated mice with 
      cardiac-specific expression of sFas and double homozygous transgenic mice that 
      express both MCP-1 and sFas. Cardiac-specific expression of sFas in MCP mice, in 
      fact, inhibited apoptosis of infiltrating mononuclear cells, normalized 
      circulating C-reactive protein (CRP) levels, and prevented macrophage activation 
      as well as production of proinflammatory cytokines, tumor necrosis factor 
      (TNF)-alpha, interleukin (IL)-1beta, and IL-6 in the hearts. sFas expression 
      resulted in restoration of cardiac structure, preservation of cardiac function, 
      and a significant prolongation of survival of MCP mice. These results demonstrate 
      that FasL released from infiltrating mononuclear cells plays a critical role in 
      the detrimental effects of MCP-1 expression, and suggest that Fas/FasL signaling 
      represents a novel therapeutic target for heart failure.
FAU - Niu, Jianli
AU  - Niu J
AD  - Biomolecular Science Center, Burnett College of Biomedical Science, University of 
      Central Florida, Orlando, FL 32816, USA.
FAU - Azfer, Asim
AU  - Azfer A
FAU - Deucher, Michael F
AU  - Deucher MF
FAU - Goldschmidt-Clermont, Pascal J
AU  - Goldschmidt-Clermont PJ
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 - 20060505
PL  - England
TA  - J Mol Cell Cardiol
JT  - Journal of molecular and cellular cardiology
JID - 0262322
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Fas Ligand Protein)
RN  - 0 (Fasl protein, mouse)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factors)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Cytokines/genetics
MH  - Fas Ligand Protein
MH  - *Gene Expression Regulation
MH  - *Gene Targeting
MH  - Heart Failure/*prevention & control
MH  - Male
MH  - Membrane Glycoproteins/chemistry/genetics/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Myocarditis/therapy
MH  - Myocardium/cytology/*metabolism/pathology
MH  - Organ Specificity
MH  - RNA, Messenger/genetics/metabolism
MH  - Solubility
MH  - Survival
MH  - Tumor Necrosis Factors/chemistry/genetics/*metabolism
MH  - Ventricular Function
PMC - PMC1523423
MID - NIHMS11268
EDAT- 2006/05/09 09:00
MHDA- 2006/08/30 09:00
PMCR- 2008/01/28
CRDT- 2006/05/09 09:00
PHST- 2006/02/03 00:00 [received]
PHST- 2006/03/15 00:00 [revised]
PHST- 2006/03/16 00:00 [accepted]
PHST- 2006/05/09 09:00 [pubmed]
PHST- 2006/08/30 09:00 [medline]
PHST- 2006/05/09 09:00 [entrez]
PHST- 2008/01/28 00:00 [pmc-release]
AID - S0022-2828(06)00085-X [pii]
AID - 10.1016/j.yjmcc.2006.03.010 [doi]
PST - ppublish
SO  - J Mol Cell Cardiol. 2006 Jun;40(6):810-20. doi: 10.1016/j.yjmcc.2006.03.010. Epub 
      2006 May 5.