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Cardiovascular Research Advance Access originally published online on June 9, 2008
Cardiovascular Research 2008 79(4):611-620; doi:10.1093/cvr/cvn154
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Post-infarct treatment with an erythropoietin–gelatin hydrogel drug delivery system for cardiac repair

Hiroyuki Kobayashi1, Shinya Minatoguchi1,*, Shinji Yasuda1, Narentuoya Bao1, Itta Kawamura1, Masamitsu Iwasa1, Takahiko Yamaki1, Syohei Sumi1, Yu Misao1, Hiroaki Ushikoshi1, Kazuhiko Nishigaki1, Genzou Takemura1, Takako Fujiwara2, Yasuhiko Tabata3 and Hisayoshi Fujiwara1

1 Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 5011194, Japan
2 Kyoto Women's University, Kyoto, Japan
3 Kyoto University, Kyoto, Japan

* Corresponding author. Tel: +81 58 230 6520; fax: +81 58 230 6524. E-mail address: minatos{at}gifu-u.ac.jp

Aims: We investigated the effect of an erythropoietin (EPO)–gelatin hydrogel drug delivery system (DDS) applied to the heart on myocardial infarct (MI) size, left ventricular (LV) remodelling and function.

Methods and results: Experiments were performed in a rabbit model of MI. The infarct size was reduced, and LV remodelling and function were improved 14 days and 2 months after MI but not at 2 days after MI in the EPO-DDS group. The number of cluster of differentiation 31(CD31)-positive microvessels and the expression of erythropoietin receptor (EPO-R), phosphorylated-Akt (p-Akt), phosphorylated glycogen synthase kinase 3β (p-GSK-3β), phosphorylated extracellular signal-regulated protein kinase (p-ERK), phosphorylated signal transducer and activator of transcription 3 (p-Stat3), vascular endothelial growth factor (VEGF), and matrix metalloproteinase-1 (MMP-1) were significantly increased in the myocardium of the EPO-DDS group.

Conclusion: Post-MI treatment with an EPO-DDS improves LV remodelling and function by activating prosurvival signalling, antifibrosis, and angiogenesis without causing any side effect.

KEYWORDS Drug delivery system; Erythropoietin; Akt; VEGF; Angiogenesis; Myocardial infarction

Time for primary review: 25 days


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