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

Cardiovasc Res. 2008 Sep 1;79(4):611-20. doi: 10.1093/cvr/cvn154. Epub 2008 Jun 9.

Abstract

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 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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / chemistry
  • Cardiovascular Agents / pharmacology*
  • Cell Survival / drug effects
  • Chemistry, Pharmaceutical
  • Disease Models, Animal
  • Dosage Forms
  • Drug Carriers
  • Erythropoietin / administration & dosage
  • Erythropoietin / chemistry
  • Erythropoietin / pharmacology*
  • Fibrosis
  • Gelatin / chemistry*
  • Humans
  • Hydrogels*
  • Immunohistochemistry
  • Injections, Subcutaneous
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Infarction / physiopathology
  • Myocardium / enzymology
  • Myocardium / pathology*
  • Neovascularization, Physiologic / drug effects
  • Rabbits
  • Recombinant Proteins
  • Signal Transduction / drug effects
  • Time Factors
  • Ventricular Function, Left / drug effects*
  • Ventricular Remodeling / drug effects*

Substances

  • Cardiovascular Agents
  • Dosage Forms
  • Drug Carriers
  • Hydrogels
  • Intracellular Signaling Peptides and Proteins
  • Recombinant Proteins
  • Erythropoietin
  • Gelatin