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Human erythropoietin gene delivery for cardiac remodeling of myocardial infarction in rats

Title
Human erythropoietin gene delivery for cardiac remodeling of myocardial infarction in rats
Author
이민형
Keywords
Gene delivery; Myocardial infarction; Remodeling; Angiotensin; BIOREDUCIBLE POLYMER SYSTEM; CLINICAL-IMPLICATIONS; EXTRACELLULAR-MATRIX; VEGF DELIVERY; TRIAL; REPERFUSION; MECHANISMS; EVOLUTION; SKELETAL; DISEASE
Issue Date
2013-07
Publisher
Elsevier Science B.V., Amsterdam.
Citation
Journal of Controlled Release, Vol.171, No.1 [2013], p24-32
Abstract
Considerable efforts have been made to exploit cardioprotective drugs and gene delivery systems for myocardial infarction (MI). The promising cardioprotective effects of recombinant human erythropoietin (rHuEPO) protein in animal experiments have not been consistently reproduced in clinical human trials of acute MI; however, the mechanisms underlying the inconsistent discrepancies are not yet fully understood. We hypothesized that the plasmid human erythropoietin gene (phEPO) delivered by our bioreducible polymer might produce cardioprotective effects on post-infarct cardiac remodeling. We demonstrated that intramyocardial delivery of phEPO by an arginine-grafted poly(disulfide amine) (ABP) polymer in infarcted rats preserves cardiac geometry and systolic function. The reduced infarct size of phEPO/ABP delivery was followed by decrease in fibrosis, protection from cardiomyocyte loss, and down-regulation of apoptotic activity. In addition, the increased angiogenesis and decreased myofibroblast density in the border zone of the infarct support the beneficial effects of phEPO/ABP administration. Furthermore, phEPO/ABP delivery induced prominent suppression on Ang II and TGF-beta activity in all subdivisions of cardiac tissues except for the central zone of infarct. These results of phEPO gene therapy delivered by a bioreducible ABP polymer provide insight into the lack of phEPO gene therapy translation in the treatment of acute MI to human trials.
URI
http://www.sciencedirect.com/science/article/pii/S0168365913003696?via%3Dihubhttp://hdl.handle.net/20.500.11754/44066
ISSN
0168-3659
DOI
10.1016/j.jconrel.2013.06.022
Appears in Collections:
COLLEGE OF ENGINEERING[S](공과대학) > BIOENGINEERING(생명공학과) > Articles
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