Erythropoietin has an antiapoptotic effect after myocardial infarction and stimulates in vitro aortic ring sprouting.
Aims were to explore if darbepoietin-alpha 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 (0.8mm) were cultured in matrigel and the angiogenic sprouting was studied after addition of darbepoietin-alpha with and without VEGF-165. After 12 days the hemoglobin concentration was 25% higher in the darbepoietin-alpha treated mice than in the control group. No difference in capillary densities in the periinfarct or noninfarcted areas was seen with darbepoietin-alpha. Cell proliferation was about 10 times higher in the periinfarct area than in the noninfarcted wall. Darbepoietin-alpha 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-alpha and VEGF-165 both independently induced sprouting from aortic rings. The results suggest that darbepoietin-alpha can induce angiogenesis but that moderate doses after myocardial infarction are not angiogenic but antiapoptotic.
Broberg
Agneta Månsson
AM
Department of Cardiology, M52 Karolinska University Hospital, S14186 Stockholm, Sweden.
Grinnemo
Karl-Henrik
KH
Genead
Rami
R
Danielsson
Christian
C
Andersson
Agneta B
AB
Wärdell
Eva
E
Sylvén
Christer
C
D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000818:Animals; D001011:Aorta / Q000187:drug effects; D017209:Apoptosis / Q000187:drug effects*; D001681:Biological Assay; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D000068256:Darbepoetin alfa; D004921:Erythropoietin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000627:therapeutic use
D043925:Angiogenesis Inducing Agents; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D004921:Erythropoietin; D000068256:Darbepoetin alfa