Adrenomedullin exerts not only vasodilatory effects, but also angiogenic effects. In the present study, we investigated the effects of adrenomedullin on collateral formation and circulating bone-marrow-derived cells after acute tissue ischaemia. Bone marrow of 8–10-week-old female C57BL/6J mice was replaced with that from GFP (green fluorescent protein) transgenic mice (GFP mice). At 8 weeks after transplantation, hindlimb ischaemia was induced by resecting the right femoral artery and a plasmid expressing human adrenomedullin (50 μg) was injected into the ischaemic muscle, followed by in vivo electroporation on a weekly basis. Overexpression of adrenomedullin significantly enhanced the blood flow recovery compared with controls (blood flow ratio, 1.0±0.2 compared with 0.6±0.3 respectively, at week 4; P<0.05) and increased capillary density in the ischaemic leg as determined by anti-CD31 immunostaining of the ischaemic muscle (567±40 compared with 338±65 capillaries/mm2 respectively, at week 5; P<0.05). There were more GFP-positive cells in the thigh muscle of the mice injected with adrenomedullin than in that of the control mice (29.6±4.5 compared with 16.5±3.3 capillaries/mm2 respectively, at week 5; P<0.05). We repeated the same experiments using LacZ-knock-in mice instead of GFP mice, and obtained similar results. These findings suggest that adrenomedullin may augment ischaemia-induced collateral formation with some effects on circulating bone-marrow-derived cells.
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December 2006
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Research Article|
November 14 2006
Effects of adrenomedullin on acute ischaemia-induced collateral development and mobilization of bone-marrow-derived cells
Minami Abe
;
Minami Abe
*Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan
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Masataka Sata
;
Masataka Sata
*Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan
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Etsu Suzuki
;
Etsu Suzuki
†Department of Nephrology and Endocrinology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan
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Ryo Takeda
;
Ryo Takeda
*Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan
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Masao Takahashi
;
Masao Takahashi
*Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan
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Hiroaki Nishimatsu
;
Hiroaki Nishimatsu
‡Department of Urology, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan
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Daisuke Nagata
;
Daisuke Nagata
*Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan
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Kenji Kangawa
;
Kenji Kangawa
§National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Hisayuki Matsuo
;
Hisayuki Matsuo
§National Cardiovascular Center Research Institute, Osaka 565-8565, Japan
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Ryozo Nagai
;
Ryozo Nagai
*Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan
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Yasunobu Hirata
*Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo 113-8655, Japan
Correspondence: Dr Yasunobu Hirata (email hirata-2im@h.u-tokyo.ac.jp).
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Clin Sci (Lond) (2006) 111 (6): 381–387.
Article history
Received:
June 05 2006
Revision Received:
August 14 2006
Accepted:
August 22 2006
Accepted Manuscript online:
August 22 2006
Citation
Minami Abe, Masataka Sata, Etsu Suzuki, Ryo Takeda, Masao Takahashi, Hiroaki Nishimatsu, Daisuke Nagata, Kenji Kangawa, Hisayuki Matsuo, Ryozo Nagai, Yasunobu Hirata; Effects of adrenomedullin on acute ischaemia-induced collateral development and mobilization of bone-marrow-derived cells. Clin Sci (Lond) 1 December 2006; 111 (6): 381–387. doi: https://doi.org/10.1042/CS20060137
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