Tumor-necrosis-factor-alpha-gene-deficient mice have improved cardiac function through reduction of intercellular adhesion molecule-1 in myocardial infarction.
BACKGROUND
Tumor necrosis factor (TNF)-alpha is linked to the pathogenesis of cardiovascular diseases, but how it affects myocardial infarction (MI), so the present study examined the effects of TNF-alpha and the involvement of intercellular adhesion molecule (ICAM)-1 on MI.


RESULTS
Left coronary arteries of C57BL/6 wild type (WT) and TNF-alpha knockout (KO) mice were ligated and the mice were killed 1, 3, and 7 days later. Fractional shortening on echocardiography of the KO mice was significantly higher than that of the WT mice from day 1 to 7 (p<0.01). The ICAM-1 mRNA in the infarcted area of the KO mice was significantly lower than that of the WT from day 1 (p<0.01) to 7. In immunohistochemistry, the expression of ICAM-1 was weaker in the KO than in the WT mice. The number of neutrophils in the KO mice peaked at day 1, but even this peak level failed to reach the levels in the infarcted (p<0.01) and peri-infarcted areas (p<0.05) in the WT. The number of macrophages in the KO mice peaked at day 7, but this peak level failed to reach the levels in the infarcted (p<0.01) and peri-infarcted areas (p<0.05) in the WT.


CONCLUSIONS
In a permanent occlusion model of MI TNF-alpha decreased cardiac function and ameliorated myocardial remodeling through the induction of ICAM-1.
Sato
Takatoshi
T
Third Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
Suzuki
Hiroshi
H
Shibata
Masayuki
M
Kusuyama
Taro
T
Omori
Yasutoshi
Y
Soda
Teruko
T
Shoji
Makoto
M
Iso
Yoshitaka
Y
Koba
Shinji
S
Geshi
Eiichi
E
Katagiri
Takashi
T
Shioda
Seiji
S
Sekikawa
Kenji
K
D000818:Animals; D004452:Echocardiography; D006321:Heart / Q000502:physiology*; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008264:Macrophages / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism / Q000503:physiopathology*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009504:Neutrophils / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1