Journal
JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART A
Volume 102, Issue 10, Pages 3452-3458Publisher
WILEY
DOI: 10.1002/jbm.a.35014
Keywords
thermosensitive hydrogel; angiotensin converting enzyme; RNA interference; myocardial infarction; remodeling
Funding
- National Nature Science Foundation of China [81170307]
- National Key Basic Research Program of China [2005CB623903]
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The expression of foreign gene was enhanced and prolonged by sustained releasing a target gene to cells from biodegradable dextran-poly(e-caprolactone)-2-hydroxylethylmethacrylate-poly(N-isopropylacrylamide) (Dex-PCL-HEMA/PNIPAAm) hydrogel in vitro. Moreover, we have demonstrated that injection of the same hydrogel improved post-infarct ventricular remodeling. Therefore, we hypothesized that intramyocardial injection of plasmid containing the short-hairpin RNA (shRNA) of angiotensin converting enzyme (ACE) with the same hydrogel enhances the cardioprotective effects superior to either alone or after rat myocardial infarction (MI). In this study, equal volume of phosphate-buffered solution (PBS), 10 mu g ACE-shRNA plasmids, hydrogel containing 10 mu g negative control ACE-shRNA plasmids and hydrogel containing 10 mu g ACE-shRNA plasmids were shortly injected into the infarct area of rats after MI, respectively. We found that ACE-shRNA plasmid-loaded hydrogel extended the duration of gene expression in vivo. Moreover, it was shown that direct intramyocardial injection of ACE-shRNA plasmid-loaded hydrogel significantly decreased the expression of local ACE expression, inhibited cell apoptosis, reduced infarct size, and improved cardiac function compared with the injection of either alone 30 days after MI in rats. These results suggest that injection of ACE-shRNA plasmid-loaded hydrogel into impaired myocardium obtains more cardioprotective effects than either alone in rat with MI by prolonging the gene silencing of ACE. (C) 2013 Wiley Periodicals, Inc.
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