Upregulation of coronary endothelial P-selectin in a monkey heart ischemia reperfusion model
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The design of targeted ultrasound contrast agents for molecular imaging of myocardial ischemia–reperfusion (IR) requires the availablity of an adequate in vivo model in a species in which cross reactivity with the target occurs. P-selectin (Psel) is an activation-dependent endothelial receptor that supports rapid and reversible cell adhesion in a flowing system. Together with E- and L-selectins it constitutes the selectin family of adhesion molecules. We investigated the myocardial expression of selectins in a closed chest minimally invasive monkey myocardial IR model. Catheter-based occlusion (30–50 min) followed by reperfusion (3 or 5 h) of left anterior descending artery (LAD) was performed in anesthetised monkeys. At the end of each procedure animals were killed, and their hearts were excised. The tissues were analyzed immunohistochemically using an anti-human Psel antibody (AK-6 clone) that cross reacts with rhesus monkey. Histopathological features confirm the presence of IR injuries in myocardial tissues. There was significant increase in the Psel expression in vessels from the IR areas. However, significantly higher Psel immunoreactivity was also seen in areas which are distant from IR injuries.
KeywordsP-selectin Occlusion Myocardium Ischemia Reperfusion Inflammation
The authors would like to thank Martine Roudier MD., PhD (Department of Pathology, University of Washington and Amgen Inc., Seattle, WA) who carried out quantitative immunohistochemical evaluations in this study. We express our personal appreciation of the valuable technical assistance given by Alexandre Helbert (Bracco Research SA, Geneva) and by the personnel at Cynbiose (Institut Claude Bourgelat, National Veterinary School of Lyon, Marcy l’Etoile, France).
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