TY - JOUR
T1 - Inhibition of adhesion molecules markedly ameliorates cytokine-induced sustained myocardial dysfunction in dogs in vivo
AU - Momii, Hidetoshi
AU - Shimokawa, Hiroaki
AU - Oyama, Jun Ichi
AU - Cheng, Xiao Shu
AU - Nakamura, Ryo
AU - Egashira, Kensuke
AU - Nakazawa, Hiroe
AU - Takeshita, Akira
N1 - Funding Information:
The authors wish to thank S. Tojo, Sumitomo Pharmaceutical Research Center, Osaka, Japan, and Y. Ohmoto and M. Ikeda, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan, for co-operation in this study, and Dr. C. W. Smith, Texas Children’s Hospital, Houston, USA, for the generous gift of a specific antibody and cDNA probe to canine P-selectin. This work was supported in part by grants from the Japanese Ministry of Education, Science, Sports and Culture, Tokyo, Japan, and by grant-in-aid from the Pfizer Foundation for Cardiovascular Research, Tokyo, Japan.
PY - 1998/12
Y1 - 1998/12
N2 - Adhesion molecules are key molecules for inflammatory cardiovascular diseases and are known to be up-regulated by inflammatory cytokines. However, the role of adhesion molecules in the cytokine-induced myocardial dysfunction in vivo remains unclear. This role was examined in our novel canine model, in which chronic treatment of the heart with IL-1β-bound microspheres (MS), but not control MS, causes sustained myocardial dysfunction in vivo. The expression of P-selectin (mRNA and immunoreactivity) was more prominent in the IL-1β group than in the control group (treated with control MS alone) after MS injection. The extent of neutrophil infiltration and myocardial myeloperoxidase (MPO) activity were significantly increased in the IL-1β group (P < 0.01). Pre-treatment with SLeX-OS (a novel oligosaccharide analog of sialyl Lewis(X)) or PB1.3 (a monoclonal antibody to P-selectin) prevented the myocardial dysfunction and significantly suppressed the neutrophil infiltration and the increase in myocardial MPO activity induced by IL-1β (P < 0.01 each). These results indicate that adhesion molecules play an important role in the pathogenesis of the cytokine-induced sustained myocardial dysfunction in dogs in vivo.
AB - Adhesion molecules are key molecules for inflammatory cardiovascular diseases and are known to be up-regulated by inflammatory cytokines. However, the role of adhesion molecules in the cytokine-induced myocardial dysfunction in vivo remains unclear. This role was examined in our novel canine model, in which chronic treatment of the heart with IL-1β-bound microspheres (MS), but not control MS, causes sustained myocardial dysfunction in vivo. The expression of P-selectin (mRNA and immunoreactivity) was more prominent in the IL-1β group than in the control group (treated with control MS alone) after MS injection. The extent of neutrophil infiltration and myocardial myeloperoxidase (MPO) activity were significantly increased in the IL-1β group (P < 0.01). Pre-treatment with SLeX-OS (a novel oligosaccharide analog of sialyl Lewis(X)) or PB1.3 (a monoclonal antibody to P-selectin) prevented the myocardial dysfunction and significantly suppressed the neutrophil infiltration and the increase in myocardial MPO activity induced by IL-1β (P < 0.01 each). These results indicate that adhesion molecules play an important role in the pathogenesis of the cytokine-induced sustained myocardial dysfunction in dogs in vivo.
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U2 - 10.1006/jmcc.1998.0820
DO - 10.1006/jmcc.1998.0820
M3 - Article
C2 - 9990535
AN - SCOPUS:0032441402
SN - 0022-2828
VL - 30
SP - 2637
EP - 2650
JO - Journal of Molecular and Cellular Cardiology
JF - Journal of Molecular and Cellular Cardiology
IS - 12
ER -
