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Combined treatment with erythropoietin and granulocyte colony-stimulating factor enhances neovascularization and improves cardiac function after myocardial infarction.
Chin Med J (Engl). 2014; 127(9):1677-83.CM

Abstract

BACKGROUND

Erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) are both potential novel therapeutics for use after myocardial infarction (MI). However, their underlying mechanisms remain unclear and the efficacy of monotherapy with EPO or G-CSF is also controversial. Therefore, we investigated the effects of combined treatment with EPO and G-CSF on neovascularization and cardiac function in post-infarction rats and explored the potential mechanisms.

METHODS

Four groups of rats were used: control (saline injection after MI, i.h.), EPO (a single dose of 5 000 IU/kg after MI, i.h.), G-CSF (a dose of 50 µg× kg(-1)× d(-1) for 5 days after MI, i.h.), and both EPO and G-CSF (EPO+G-CSF, using the same regiment as above). Cardiac function was assessed by echocardiography before and 1 day, 7 days, 14 days and 21 days after MI. CD34(+)/Flk-1(+) cells in the peripheral blood were evaluated by flow cytometry before and 3 days, 5 days and 7 days after MI. The infarct area and angiogenesis in the peri-infarct area were analyzed. The mRNA and protein expression of vascular endothelial growth factor (VEGF) and stromal-derived factor-1a (SDF-1α) in the peri-infarct area were detected by real-time quantitative RT-PCR and Western blotting.

RESULTS

Compared with the control and monotherapy groups, the EPO+G-CSF group had significantly increased CD34(+)/Flk-1(+) endothelial progenitor cells (EPCs) in the peripheral blood (P < 0.05), up-regulated VEGF and SDF-1α levels in the peri-infarct region (P < 0.05), enhanced capillary density (P < 0.05), reduced infarct size (P < 0.05) and improved cardiac structure and function (P < 0.05). G-CSF alone did not dramatically increase EPCs in the peripheral blood, enhance capillary density in the peri-infarct area or reduce infarct size compared with the control group.

CONCLUSIONS

Combined treatment with EPO and G-CSF increased EPCs mobilization, up-regulated VEGF and SDF-1α levels in the post-infarction microenvironment, subsequently enhanced neovascularization in the peri-infarct region and reduced infarct size. All factors contributed to its beneficial effects on cardiac function in post-infarction rats.

Authors+Show Affiliations

Department of Cardiology, the First Clinical Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China.Department of Ultrasound, the Second Clinical Hospital, Harbin Medical University, Harbin, Heilongjiang 150086 China.Department of Cardiology, the First Clinical Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China.Department of Cardiology, the First Clinical Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China.Department of Cardiovascular Medicine, Nippon Medical School, Tokyo, Japan.Department of Cardiology, the First Clinical Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China.Department of Cardiology, the First Clinical Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China.Department of Cardiology, the First Clinical Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China.Department of Cardiology, the First Clinical Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China.Department of Cardiology, the First Clinical Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China.Department of Cardiology, the First Clinical Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, China. Email: xuejingyi72@163.com.

Pub Type(s)

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

Language

eng

PubMed ID

24791874

Citation

Xue, Jingyi, et al. "Combined Treatment With Erythropoietin and Granulocyte Colony-stimulating Factor Enhances Neovascularization and Improves Cardiac Function After Myocardial Infarction." Chinese Medical Journal, vol. 127, no. 9, 2014, pp. 1677-83.
Xue J, Du G, Shi J, et al. Combined treatment with erythropoietin and granulocyte colony-stimulating factor enhances neovascularization and improves cardiac function after myocardial infarction. Chin Med J (Engl). 2014;127(9):1677-83.
Xue, J., Du, G., Shi, J., Li, Y., Yasutake, M., Liu, L., Li, J., Kong, Y., Wang, S., Yun, F., & Li, W. (2014). Combined treatment with erythropoietin and granulocyte colony-stimulating factor enhances neovascularization and improves cardiac function after myocardial infarction. Chinese Medical Journal, 127(9), 1677-83.
Xue J, et al. Combined Treatment With Erythropoietin and Granulocyte Colony-stimulating Factor Enhances Neovascularization and Improves Cardiac Function After Myocardial Infarction. Chin Med J (Engl). 2014;127(9):1677-83. PubMed PMID: 24791874.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Combined treatment with erythropoietin and granulocyte colony-stimulating factor enhances neovascularization and improves cardiac function after myocardial infarction. AU - Xue,Jingyi, AU - Du,Guoqing, AU - Shi,Jing, AU - Li,Yue, AU - Yasutake,Masahiro, AU - Liu,Lei, AU - Li,Jianqiang, AU - Kong,Yihui, AU - Wang,Shuxian, AU - Yun,Fengxiang, AU - Li,Weimin, PY - 2014/5/6/entrez PY - 2014/5/6/pubmed PY - 2015/4/7/medline SP - 1677 EP - 83 JF - Chinese medical journal JO - Chin Med J (Engl) VL - 127 IS - 9 N2 - BACKGROUND: Erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) are both potential novel therapeutics for use after myocardial infarction (MI). However, their underlying mechanisms remain unclear and the efficacy of monotherapy with EPO or G-CSF is also controversial. Therefore, we investigated the effects of combined treatment with EPO and G-CSF on neovascularization and cardiac function in post-infarction rats and explored the potential mechanisms. METHODS: Four groups of rats were used: control (saline injection after MI, i.h.), EPO (a single dose of 5 000 IU/kg after MI, i.h.), G-CSF (a dose of 50 µg× kg(-1)× d(-1) for 5 days after MI, i.h.), and both EPO and G-CSF (EPO+G-CSF, using the same regiment as above). Cardiac function was assessed by echocardiography before and 1 day, 7 days, 14 days and 21 days after MI. CD34(+)/Flk-1(+) cells in the peripheral blood were evaluated by flow cytometry before and 3 days, 5 days and 7 days after MI. The infarct area and angiogenesis in the peri-infarct area were analyzed. The mRNA and protein expression of vascular endothelial growth factor (VEGF) and stromal-derived factor-1a (SDF-1α) in the peri-infarct area were detected by real-time quantitative RT-PCR and Western blotting. RESULTS: Compared with the control and monotherapy groups, the EPO+G-CSF group had significantly increased CD34(+)/Flk-1(+) endothelial progenitor cells (EPCs) in the peripheral blood (P < 0.05), up-regulated VEGF and SDF-1α levels in the peri-infarct region (P < 0.05), enhanced capillary density (P < 0.05), reduced infarct size (P < 0.05) and improved cardiac structure and function (P < 0.05). G-CSF alone did not dramatically increase EPCs in the peripheral blood, enhance capillary density in the peri-infarct area or reduce infarct size compared with the control group. CONCLUSIONS: Combined treatment with EPO and G-CSF increased EPCs mobilization, up-regulated VEGF and SDF-1α levels in the post-infarction microenvironment, subsequently enhanced neovascularization in the peri-infarct region and reduced infarct size. All factors contributed to its beneficial effects on cardiac function in post-infarction rats. SN - 2542-5641 UR - https://www.unboundmedicine.com/medline/citation/24791874/Combined_treatment_with_erythropoietin_and_granulocyte_colony_stimulating_factor_enhances_neovascularization_and_improves_cardiac_function_after_myocardial_infarction_ L2 - https://Insights.ovid.com/pubmed?pmid=24791874 DB - PRIME DP - Unbound Medicine ER -