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Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis.
FASEB J. 2009 Feb; 23(2):351-61.FJ

Abstract

Mobilization of bone marrow-derived stem cells (BMCs) was shown to have protective effects after myocardial infarction (MI). However, the classical mobilizing agent, granulocyte-colony stimulating factor (G-CSF) relapsed after revealing an impaired homing capacity. In the search for superior cytokines, erythropoietin (EPO) appears to be a promising agent. Therefore, we analyzed in a murine model of surgically induced MI the influence of EPO treatment on survival and functional parameters as well as BMC mobilization, homing, and effect on resident cardiac stem cells (CSCs). Human EPO was injected intraperitoneally after ligation of the left anterior descendens (LAD) for 3 days with a total dose of 5000 IU/kg 6 and 30 days after MI, and pressure volume relationships were investigated in vivo. Cardiac tissues were analyzed by histology. To show the effect on BMCs and CSCs, FACS analyses were performed. Homing factors were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and ELISA. EPO-treated animals showed a significant improvement of survival post-MI (62 vs. 36%). At days 6 and 30, all hemodynamic parameters associated with attenuated remodeling, enhanced neovascularization, and diminished apoptotic cells in the peri-infarct area were improved. BMC subpopulations (CD31(+), c-kit(+), and Sca-1(+) cells) were mobilized, and homing of Sca-1(+) and CXCR4(+) BMCs toward an SDF-1 gradient into the ischemic myocardium was enhanced. However, there was no beneficial effect on CSCs. We have shown that EPO application after MI shows cardioprotective effects. This may be explained by mobilization of BMCs, which are homing via the CXCR-4/SDF-1 axis. However, EPO has no beneficial effects on resident CSCs. Therefore, new treatment regimes using EPO together with other agents may combine complementary beneficial effects preventing ischemic cardiomyopathy.

Authors+Show Affiliations

Klinikum Grosshadern, Medical Department I, Munich, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18827024

Citation

Brunner, Stefan, et al. "Erythropoietin Administration After Myocardial Infarction in Mice Attenuates Ischemic Cardiomyopathy Associated With Enhanced Homing of Bone Marrow-derived Progenitor Cells Via the CXCR-4/SDF-1 Axis." FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, vol. 23, no. 2, 2009, pp. 351-61.
Brunner S, Winogradow J, Huber BC, et al. Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis. FASEB J. 2009;23(2):351-61.
Brunner, S., Winogradow, J., Huber, B. C., Zaruba, M. M., Fischer, R., David, R., Assmann, G., Herbach, N., Wanke, R., Mueller-Hoecker, J., & Franz, W. M. (2009). Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis. FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology, 23(2), 351-61. https://doi.org/10.1096/fj.08-109462
Brunner S, et al. Erythropoietin Administration After Myocardial Infarction in Mice Attenuates Ischemic Cardiomyopathy Associated With Enhanced Homing of Bone Marrow-derived Progenitor Cells Via the CXCR-4/SDF-1 Axis. FASEB J. 2009;23(2):351-61. PubMed PMID: 18827024.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Erythropoietin administration after myocardial infarction in mice attenuates ischemic cardiomyopathy associated with enhanced homing of bone marrow-derived progenitor cells via the CXCR-4/SDF-1 axis. AU - Brunner,Stefan, AU - Winogradow,Janina, AU - Huber,Bruno C, AU - Zaruba,Marc-Michael, AU - Fischer,Rebekka, AU - David,Robert, AU - Assmann,Gerald, AU - Herbach,Nadja, AU - Wanke,Ruediger, AU - Mueller-Hoecker,Josef, AU - Franz,Wolfgang-Michael, Y1 - 2008/09/30/ PY - 2008/10/2/pubmed PY - 2009/2/17/medline PY - 2008/10/2/entrez SP - 351 EP - 61 JF - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JO - FASEB J VL - 23 IS - 2 N2 - Mobilization of bone marrow-derived stem cells (BMCs) was shown to have protective effects after myocardial infarction (MI). However, the classical mobilizing agent, granulocyte-colony stimulating factor (G-CSF) relapsed after revealing an impaired homing capacity. In the search for superior cytokines, erythropoietin (EPO) appears to be a promising agent. Therefore, we analyzed in a murine model of surgically induced MI the influence of EPO treatment on survival and functional parameters as well as BMC mobilization, homing, and effect on resident cardiac stem cells (CSCs). Human EPO was injected intraperitoneally after ligation of the left anterior descendens (LAD) for 3 days with a total dose of 5000 IU/kg 6 and 30 days after MI, and pressure volume relationships were investigated in vivo. Cardiac tissues were analyzed by histology. To show the effect on BMCs and CSCs, FACS analyses were performed. Homing factors were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and ELISA. EPO-treated animals showed a significant improvement of survival post-MI (62 vs. 36%). At days 6 and 30, all hemodynamic parameters associated with attenuated remodeling, enhanced neovascularization, and diminished apoptotic cells in the peri-infarct area were improved. BMC subpopulations (CD31(+), c-kit(+), and Sca-1(+) cells) were mobilized, and homing of Sca-1(+) and CXCR4(+) BMCs toward an SDF-1 gradient into the ischemic myocardium was enhanced. However, there was no beneficial effect on CSCs. We have shown that EPO application after MI shows cardioprotective effects. This may be explained by mobilization of BMCs, which are homing via the CXCR-4/SDF-1 axis. However, EPO has no beneficial effects on resident CSCs. Therefore, new treatment regimes using EPO together with other agents may combine complementary beneficial effects preventing ischemic cardiomyopathy. SN - 1530-6860 UR - https://www.unboundmedicine.com/medline/citation/18827024/Erythropoietin_administration_after_myocardial_infarction_in_mice_attenuates_ischemic_cardiomyopathy_associated_with_enhanced_homing_of_bone_marrow_derived_progenitor_cells_via_the_CXCR_4/SDF_1_axis_ L2 - https://doi.org/10.1096/fj.08-109462 DB - PRIME DP - Unbound Medicine ER -