The inhibition of postinfarct ventricle remodeling without polycythaemia following local sustained intramyocardial delivery of erythropoietin within a supramolecular hydrogel.
Erythropoietin (EPO) can protect myocardium from ischemic injury, but it also plays an important role in promoting polycythaemia, the potential for thrombo-embolic complications. Local sustained delivery of bioactive agents directly to impaired tissues using biomaterials is an approach to limit systemic toxicity and improve the efficacy of therapies. The present study was performed to investigate whether local intramyocardial injection of EPO with hydrogel could enhance cardioprotective effect without causing polycythaemia after myocardial infarction (MI). To test the hypothesis, phosphate buffered solution (PBS), alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel, recombined human erythropoietin (rhEPO) in PBS, or rhEPO in hydrogel were injected into the infarcted area immediately after MI in rats. The hydrogel allowed a sustained release of EPO, which inhibited cell apoptosis and increased neovasculature formation, and subsequently reduced infarct size and improved cardiac function compared with other groups. Notably, there was no evidence of polycythaemia from this therapy, with no differences in erythrocyte count and hematocrit compared with the animals received PBS or hydrogel blank injection. In conclusion, intramyocardial delivery of rhEPO with alpha-cyclodextrin/MPEG-PCL-MPEG hydrogel may lead to cardiac performance improvement after MI without apparent adverse effect.
Wang
Tao
T
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
Jiang
Xue-Jun
XJ
Lin
Tao
T
Ren
Shan
S
Li
Xiao-Yan
XY
Zhang
Xian-Zheng
XZ
Tang
Qi-zhu
QZ
D000818:Animals; D017209:Apoptosis; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D004452:Echocardiography; D004921:Erythropoietin / Q000009:adverse effects / Q000627:therapeutic use; D006439:Hemodynamics; D006801:Humans; D020100:Hydrogels / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008422:Materials Testing; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D009206:Myocardium / Q000166:cytology; D018919:Neovascularization, Physiologic; D011086:Polycythemia / Q000139:chemically induced*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000502:physiology; D020257:Ventricular Remodeling / Q000502:physiology*; D047391:alpha-Cyclodextrins / Q000737:chemistry / Q000378:metabolism
D001672:Biocompatible Materials; D002316:Cardiotonic Agents; D004337:Drug Carriers; D020100:Hydrogels; D047391:alpha-Cyclodextrins; D004921:Erythropoietin; C032613:alpha-cyclodextrin