Enhanced cardioprotective effects mediated by plasmid containing the short-hairpin RNA of angiotensin converting enzyme with a biodegradable hydrogel after myocardial infarction.
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 μg ACE-shRNA plasmids, hydrogel containing 10 μg negative control ACE-shRNA plasmids and hydrogel containing 10 μg 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. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3452-3458, 2014.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, 430060, People's Republic of China; Cardiovascular Research Institute, Wuhan University, Wuhan, 430060, People's Republic of China.
Wei-Guo
WG
Wan
Xue-Jun
XJ
Jiang
Xiao-Yan
XY
Li
Cui
C
Zhang
Xin
X
Yi
Shan
S
Ren
Xian-Zheng
XZ
Zhang
D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001672:Biocompatible Materials / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D044367:Phase Transition / Q000187:drug effects; D010957:Plasmids / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism*; D017208:Rats, Wistar; D013696:Temperature; D014463:Ultrasonography
D001672:Biocompatible Materials; D002316:Cardiotonic Agents; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D000804:Angiotensin II; D049452:Green Fluorescent Proteins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D007703:Peptidyl-Dipeptidase A
RNA interference; angiotensin converting enzyme; myocardial infarction; remodeling; thermosensitive hydrogel