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

doi:10.1093/cvr/cvn154

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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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)–gelatinhydrogel drug delivery system (DDS) applied to the heart onmyocardial infarct (MI) size, left ventricular (LV) remodellingand function.

Methods and results: Experiments were performed in a rabbit model of MI. The infarctsize was reduced, and LV remodelling and function were improved14 days and 2 months after MI but not at 2 days after MI inthe EPO-DDS group. The number of cluster of differentiation31(CD31)-positive microvessels and the expression of erythropoietinreceptor (EPO-R), phosphorylated-Akt (p-Akt), phosphorylatedglycogen synthase kinase 3β (p-GSK-3β), phosphorylatedextracellular signal-regulated protein kinase (p-ERK), phosphorylatedsignal 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 theEPO-DDS group.

Conclusion: Post-MI treatment with an EPO-DDS improves LV remodelling andfunction 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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