Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-14434
Camici, G G; Stallmach, T; Hermann, M; Hassink, R; Doevendans, P; Grenacher, B; Hirschy, A; Vogel, J; Lüscher, T F; Ruschitzka, F; Gassmann, M (2007). Constitutively overexpressed erythropoietin reduces infarct size in a mouse model of permanent coronary artery ligation. Methods in Enzymology, 435:147-155.
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In view of the emerging role of recombinant human erythropoietin (rhEPO) as a novel therapeutical approach in myocardial ischemia, we performed the first two-way parallel comparison to test the effects of rhEPO pretreatment (1000 U/kg, 12h before surgery) versus EPO transgenic overexpression in a mouse model of myocardial infarction. Unlike EPO transgenic mice who doubled their hematocrit, rhEPO pretreated mice maintained an unaltered hematocrit, thereby offering the possibility to discern erythropoietic-dependent from erythropoietic-independent protective effects of EPO. Animals pretreated with rhEPO as well as EPO transgenic mice underwent permanent left anterior descending (LAD) coronary artery ligation. Resulting infarct size was determined 24h after LAD ligation by hematoxylin/eosin staining, and morphometrical analysis was performed by computerized planimetry. A large reduction in infarction size was observed in rhEPO-treated mice (-74% +/- 14.51; P = 0.0002) and an even more pronounced reduction in the EPO transgenic group (-87% +/- 6.31; P < 0.0001) when compared to wild-type controls. Moreover, while searching for novel early ischemic markers, we analyzed expression of hypoxia-sensitive Wilms' tumor suppressor gene (WT1) in infarcted hearts. We found that its expression correlated with the infarct area, thereby providing the first demonstration that WT1 is a useful early marker of myocardial infarction. This study demonstrates for the first time that, despite high hematocrit levels, endogenously overexpressed EPO provides protection against myocardial infarction in a murine model of permanent LAD ligation.
|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Physiology|
07 Faculty of Science > Institute of Physiology
04 Faculty of Medicine > Center for Integrative Human Physiology
05 Vetsuisse Faculty > Institute of Veterinary Physiology
04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
|DDC:||570 Life sciences; biology|
610 Medicine & health
|Deposited On:||15 Mar 2009 21:24|
|Last Modified:||21 Dec 2012 20:51|
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