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


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 3beta (p-GSK-3beta), 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.


CONCLUSIONS
Post-MI treatment with an EPO-DDS improves LV remodelling and function by activating prosurvival signalling, antifibrosis, and angiogenesis without causing any side effect.
Department of Cardiology, Gifu University Graduate School of Medicine, Yanagido 1-1, Gifu 5011194, Japan.
Hiroyuki
H
Kobayashi
Shinya
S
Minatoguchi
Shinji
S
Yasuda
Narentuoya
N
Bao
Itta
I
Kawamura
Masamitsu
M
Iwasa
Takahiko
T
Yamaki
Syohei
S
Sumi
Yu
Y
Misao
Hiroaki
H
Ushikoshi
Kazuhiko
K
Nishigaki
Genzou
G
Takemura
Takako
T
Fujiwara
Yasuhiko
Y
Tabata
Hisayoshi
H
Fujiwara
D000818:Animals; D015153:Blotting, Western; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D004195:Disease Models, Animal; D004304:Dosage Forms; D004337:Drug Carriers; D004921:Erythropoietin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005355:Fibrosis; D005780:Gelatin / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels; D007150:Immunohistochemistry; D007279:Injections, Subcutaneous; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000201:enzymology / Q000473:pathology*; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011817:Rabbits; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects*; D020257:Ventricular Remodeling / Q000187:drug effects*
D002317:Cardiovascular Agents; D004304:Dosage Forms; D004337:Drug Carriers; D020100:Hydrogels; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D004921:Erythropoietin; D005780:Gelatin