Reduction of rat myocardial ischaemia/reperfusion injury by a synthetic selectin oligopeptide.
Neutrophils infiltrate into myocardial tissue subjected to ischaemia followed by reperfusion and play a major role in myocardial reperfusion injury. The infiltration of neutrophils begins within 2 h after reperfusion, indicating the engagement of rapidly inducible adhesion molecules, such as P-selectin, on vascular endothelial cells of myocardial tissue. To investigate the essential role of P-selectin in myocardial reperfusion injury, this study examined the expression of P-selectin in rat hearts subjected to 30 min of ischaemia followed by reperfusion. The induction of P-selectin was also evaluated on the surface of cultured rat vascular endothelial cells subjected to 60 min of hypoxia, followed by reoxygenation in vitro. Finally, the effects of in vivo administration of a synthetic selectin oligopeptide on myocardial necrosis were analysed. Reperfusion of ischaemic myocardial tissue resulted in enhanced expression of P-selectin on the luminal surface of vascular endothelium and surface expression of P-selectin was induced on cultured vascular endothelial cells by hypoxia/reoxygenation in vitro. The in vivo administration of a synthetic selectin oligopeptide significantly reduced the area of myocardial infarction produced by 30 min of ischaemia, followed by 48 h of reperfusion. These data offer therapeutic possibilities for acute myocardial infarction.
Seko
Y
Y
Third Department of Internal Medicine, University of Tokyo, Japan.
Enokawa
Y
Y
Nakao
T
T
Yagita
H
H
Okumura
K
K
Yazaki
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D007150:Immunohistochemistry; D008297:Male; D008969:Molecular Sequence Data; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019007:P-Selectin / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000627:therapeutic use
D019007:P-Selectin; D011994:Recombinant Proteins