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Erythropoietin has an antiapoptotic effect after myocardial infarction and stimulates in vitro aortic ring sprouting
Authors:Broberg Agneta Månsson  Grinnemo Karl-Henrik  Genead Rami  Danielsson Christian  Andersson Agneta B  Wärdell Eva  Sylvén Christer
Institution:a Department of Cardiology, M52 Karolinska University Hospital, S14186 Stockholm, Sweden
b Department of Cardiothoracic Surgery, Karolinska University Hospital, Sweden
Abstract:Aims were to explore if darbepoietin-α in mouse can induce angiogenesis and if moderate doses after myocardial infarction stimulates periinfarct capillary and arteriolar densities, cell proliferation, and apoptosis. Myocardial infarction was induced by ligation of LAD. Mouse aortic rings (0.8 mm) were cultured in matrigel and the angiogenic sprouting was studied after addition of darbepoietin-α with and without VEGF-165. After 12 days the hemoglobin concentration was 25% higher in the darbepoietin-α treated mice than in the control group. No difference in capillary densities in the periinfarct or noninfarcted areas was seen with darbepoietin-α. Cell proliferation was about 10 times higher in the periinfarct area than in the noninfarcted wall. Darbepoietin-α treatment led to a decrease of cell proliferation (BrdU, (p < 0.02)) and apoptosis (TUNEL, p < 0.005) with about 30% in the periinfarct area. Darbepoietin-α and VEGF-165 both independently induced sprouting from aortic rings. The results suggest that darbepoietin-α can induce angiogenesis but that moderate doses after myocardial infarction are not angiogenic but antiapoptotic.
Keywords:Erythropoietin  Mouse  Myocardial infarction  Angiogenesis  Apoptosis
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