Nonanticoagulant heparin inhibits NF-kappaB activation and attenuates myocardial reperfusion injury.

Abstract

Heparin reduces ischemia-reperfusion injury to myocardium. This effect has been attributed to complement inhibition, but heparin also has other activities that might diminish ischemia-reperfusion. To further probe these mechanisms, we compared heparin or an o-desulfated nonanticoagulant heparin with greatly reduced anticomplement activity. When given at the time of coronary artery reperfusion in a canine model of myocardial infarction, heparin or o-desulfated heparin equally reduced neutrophil adherence to ischemic-reperfused coronary artery endothelium, influx of neutrophils into ischemic-reperfused myocardium, myocardial necrosis, and release of creatine kinase into plasma. Heparin or o-desulfated heparin also prevented dysfunction of endothelial-dependent coronary relaxation following ischemic injury. In addition, heparin and o-desulfated heparin inhibited translocation of the transcription nuclear factor-kappaB (NF-kappaB) from the cytoplasm to the nucleus in human endothelial cells and decreased NF-kappaB DNA binding in human endothelium and ischemic-reperfused rat myocardium. Thus heparin and nonanticoagulant heparin decrease ischemia-reperfusion injury by disrupting multiple levels of the inflammatory cascade, including the novel observation that heparins inhibit activation of the proinflammatory transcription factor NF-kappaB.

• Authors: V H Thourani, S S Brar, T P Kennedy, L R Thornton, J A Watts, R S Ronson, Z Q Zhao, A L Sturrock, J R Hoidal, J Vinten-Johansen
• Journal: American journal of physiology. Heart and circulatory physiology (Am J Physiol Heart Circ Physiol) Vol. 278 Issue 6 Pg. H2084-93 (Jun 2000) ISSN: 0363-6135 [Print] United States
• PMID: 10843908 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• NF-kappa B
• heparin, O-desulfated
• Heparin

Topics

• Animals
• Arteries (drug effects, physiopathology)
• Blood Coagulation (drug effects)
• Cell Adhesion (drug effects)
• Coronary Vessels (drug effects, physiopathology)
• Dogs
• Endothelium, Vascular (drug effects, physiopathology)
• Female
• Heart (drug effects, physiopathology)
• Heparin (analogs & derivatives, pharmacology)
• Humans
• In Vitro Techniques
• Male
• Myocardial Contraction (drug effects)
• Myocardial Infarction (pathology)
• Myocardial Ischemia (physiopathology)
• Myocardial Reperfusion Injury (pathology, physiopathology)
• Myocardium (pathology)
• NF-kappa B (antagonists & inhibitors, physiology)
• Neutrophils (pathology, physiology)
• Rats
• Rats, Sprague-Dawley