徳島大学 教育・研究者情報データベース(EDB)

1. (英) Fujii Takafumi

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2. (英) Nagaya Noritoshi

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3. 岩瀬 俊

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4. (英) Murakami Shinsuke

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5. (英) Miyahara Yoshinori

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6. (英) Nishigami Kazuhiro

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7. (英) Ishibashi-Ueda Hatsue

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8. (英) Shirai Mikiyasu

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9. (英) Itoh Takefumi

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10. (英) Ishino Kozo

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11. (英) Sano Shunji

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12. 寒川 賢治(国立循環器病センター研究所)

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13. (英) Mori Hidezo

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(英) Adrenomedullin enhances therapeutic potency of bone marrow transplantation for myocardial infarction in rats

(英) Adrenomedullin (AM), a potent vasodilator, induces angiogenesis and inhibits cell apoptosis through the phosphatidylinositol 3-kinase/Akt pathway. Transplantation of bone marrow-derived mononuclear cells (MNC) induces angiogenesis. We investigated whether infusion of AM enhances the therapeutic potency of MNC transplantation in a rat model of myocardial infarction. Immediately after coronary ligation, bone marrow-derived MNC (5 x 10(6) cells) were injected into the ischemic myocardium, followed by subcutaneous administration of 0.05 microg x kg(-1) x min(-1) AM (AM-MNC group) or saline (MNC group) for 3 days. Another two groups of rats received subcutaneous administration of AM alone (AM group) or saline (control group). Hemodynamic and histological analyses were performed 4 wk after treatment. Cardiac infarct size was significantly smaller in the MNC and AM groups than in the control group. A combination of AM infusion and MNC transplantation demonstrated a further decrease in infarct size. Left ventricular (LV) maximum change in pressure over time and LV fractional shortening were significantly improved only in the AM-MNC group. AM significantly increased capillary density in ischemic myocardium, suggesting the angiogenic potency of AM. AM infusion plus MNC transplantation demonstrated a further increase in capillary density compared with AM or MNC alone. Although MNC apoptosis was frequently observed 72 h after transplantation, AM markedly decreased the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling-positive cells among the transplanted MNC. In conclusion, AM enhanced the angiogenic potency of MNC transplantation and improved cardiac function in rats with myocardial infarction. This beneficial effect may be mediated partly by the angiogenic property of AM itself and by its antiapoptotic effect on MNC.

1. (英) Adrenomedullin
2. (英) Animals
3. アポトーシス(apoptosis)
4. (英) Bone Marrow Transplantation
5. (英) Capillaries
6. 細胞分化(cell differentiation)
7. (英) Combined Modality Therapy
8. (英) Coronary Circulation
9. (英) Echocardiography
10. (英) Endothelium, Vascular
11. (英) Graft Survival
12. (英) Heart Ventricles
13. (英) Male
14. (英) Myocardial Infarction
15. 心筋(myocardium)
16. (英) Neovascularization, Physiologic
17. (英) Organ Size
18. (英) Peptides
19. (英) Rats
20. (英) Rats, Inbred Lew
21. (英) Vasodilator Agents

1. (英) Article.Affiliation: Department of Cardiac Physiology, National Cardiovascular Center, Suita, Osaka, Japan.

2. (英) Article.PublicationTypeList.PublicationType: Journal Article

3. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't