PMID- 12970235
OWN - NLM
STAT- MEDLINE
DCOM- 20030930
LR  - 20081121
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 108 Suppl 1
DP  - 2003 Sep 9
TI  - Transfection with a dominant-negative inhibitor of monocyte chemoattractant 
      protein-1 gene improves cardiac function after 6 hours of cold preservation.
PG  - II213-8
AB  - BACKGROUND: Monocyte chemoattractant protein-1 (MCP-1), a potent chemotactic 
      factor for monocytes, is induced during ischemia-reperfusion. As monocytes might 
      play an important causative role in reperfusion injury, we investigated if 
      inhibition of monocyte activation could attenuate ischemia-reperfusion injury and 
      thereby improve cardiac preservation. To inhibit monocyte activation, we 
      transfected a dominant-negative inhibitor of MCP-1 (7ND) gene in an animal model. 
      METHODS AND RESULTS: We used an isolated rabbit heart preparation perfused with 
      support-rabbit blood and transfected 7ND genes to skeletal muscle of the support 
      rabbits (n=7) using electroporation technique; causing an elevation of serum 7ND 
      level to 20+/-7 pg/mL at 5 days after transfection. Animals receiving empty 
      plasmid served as controls (n=7). Five days after transfection, hearts from other 
      rabbits were excised, stored in UW solution for 6hours, and perfused with blood 
      from transfected support rabbits. The 7ND group showed better cardiac output 
      (128.7+/-17.9 versus 81.6+/-19.8 mL/min; P<0.01), lower serum CK-MB levels 
      (5.0+/-1.8 versus 11.1+/-2.9 ng/mL; P<0.01), lower serum IL-1beta levels 
      (257.2+/-23.2 versus 311.2+/-37.4pg/mL; P<0.05), and lower serum TNF-alpha levels 
      (19.0+/-8.4 versus 35.1+/-13.0pg/mL; P<0.05). The numbers of infiltrating cells 
      in myocardium were significantly reduced in the 7ND group. CONCLUSIONS: 
      Inhibition of MCP-1 with 7ND gene transfection reduced cytokine activation, 
      attenuated myocardial damage, and improved cardiac function after 6 hours of 
      preservation. These results show that MCP-1 plays an important role in 
      ischemia-reperfusion injury.
FAU - Kajihara, Noriyoshi
AU  - Kajihara N
AD  - Department of Cardiovascular Surgery, Graduate School of Medical Sciences, Kyushu 
      University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
FAU - Morita, Shigeki
AU  - Morita S
FAU - Nishida, Takahiro
AU  - Nishida T
FAU - Tatewaki, Hideki
AU  - Tatewaki H
FAU - Eto, Masataka
AU  - Eto M
FAU - Egashira, Kensuke
AU  - Egashira K
FAU - Yasui, Hisataka
AU  - Yasui H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-1)
RN  - 0 (Isoenzymes)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.3.2 (Creatine Kinase)
RN  - EC 2.7.3.2 (Creatine Kinase, MB Form)
SB  - IM
MH  - Animals
MH  - Cell Movement
MH  - Chemokine CCL2/blood/*genetics
MH  - *Cold Temperature
MH  - Creatine Kinase/blood
MH  - Creatine Kinase, MB Form
MH  - Heart/*physiology
MH  - Interleukin-1/blood
MH  - Isoenzymes/blood
MH  - Monocytes/physiology
MH  - Mutation
MH  - Myocardial Reperfusion Injury/pathology/therapy
MH  - Myocardium/pathology
MH  - *Organ Preservation
MH  - Rabbits
MH  - Time Factors
MH  - Transfection
MH  - Tumor Necrosis Factor-alpha/analysis
MH  - Ventricular Function, Left
EDAT- 2003/09/13 05:00
MHDA- 2003/10/01 05:00
CRDT- 2003/09/13 05:00
PHST- 2003/09/13 05:00 [pubmed]
PHST- 2003/10/01 05:00 [medline]
PHST- 2003/09/13 05:00 [entrez]
AID - 108/10_suppl_1/II-213 [pii]
AID - 10.1161/01.cir.0000087426.18858.3a [doi]
PST - ppublish
SO  - Circulation. 2003 Sep 9;108 Suppl 1:II213-8. doi: 
      10.1161/01.cir.0000087426.18858.3a.