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Constitutively overexpressed erythropoietin reduces infarct size in a mouse model of permanent coronary artery ligation.
- Source :
-
Methods in enzymology [Methods Enzymol] 2007; Vol. 435, pp. 147-55. - Publication Year :
- 2007
-
Abstract
- 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.
- Subjects :
- Animals
Biomarkers analysis
Coronary Vessels
Disease Models, Animal
Erythropoietin blood
Erythropoietin genetics
Erythropoietin pharmacology
Hematocrit
Humans
Mice
Mice, Transgenic
Myocardial Infarction genetics
Recombinant Proteins
Erythropoietin metabolism
Myocardial Infarction pathology
Myocardial Infarction prevention & control
WT1 Proteins analysis
Subjects
Details
- Language :
- English
- ISSN :
- 0076-6879
- Volume :
- 435
- Database :
- MEDLINE
- Journal :
- Methods in enzymology
- Publication Type :
- Academic Journal
- Accession number :
- 17998053
- Full Text :
- https://doi.org/10.1016/S0076-6879(07)35008-8