Suppression of stent-induced tissue hyperplasia in rats by using small interfering RNA to target matrix metalloproteinase-9.
OBJECTIVE
We evaluated the efficacy of small interfering RNA (siRNA) in targeting matrix metalloproteinase (MMP-9) to suppress stent-induced tissue hyperplasia in a rat esophageal model.


METHODS
The silencing effect of the candidate siRNA (termed (MMP-9 siRNA) was evaluated in 9 L rat glial cells. Four groups of rats (n = 10, each group) were used: Eso-S, stent insertion only, comparison; Eso-R, stent insertion plus treatment with MMP-9 siRNA complexed with Chol-R9 for delivery, experimental; Eso-P, stent insertion plus treatment with pCMV-luc complexed with Chol-R9, for confirmation of Chol-R9 delivery effect; and Eso-N, no stent insertion and no treatment, controls. All rats were sacrificed at 3 weeks. The therapeutic efficacy of the MMP-9 siRNA/Chol-R9 complex was assessed.


RESULTS
The most potent MMP-9 siRNA was selected. Compared with the Eso-S group, the Eso-R group showed significantly less tissue hyperplasia with a lower percentage of granulation tissue and smaller granulation tissue area, and also significantly lower MMP-9 level.


CONCLUSIONS
MMP-9 siRNA/Chol-R9 is effective for inhibiting stent-induced tissue hyperplasia in a rat esophageal model.
Medical Device Development Center, Osong Medical Innovation Foundation, Chungbuk, Korea.
Eun-Young
EY
Kim
Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Ji Hoon
JH
Shin
Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Ho-Young
HY
Song
Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Jin Hyung
JH
Kim
Department of Radiology, UCLA Medical Center, Los Angeles, USA.
Edward W
EW
Lee
Department of Chemistry, Polymer Research Institute, Pohang University of Science and Technology, Pohang, Korea.
Won Jong
WJ
Kim
Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
Dong-Ho
DH
Shin
Department of Microbiology, Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Seoul, Korea.
Heuiran
H
Lee
D000818:Animals; D002478:Cells, Cultured; D002784:Cholesterol / Q000031:analogs & derivatives; D016503:Drug Delivery Systems; D015365:Enoxacin / Q000494:pharmacology; D004947:Esophagus / Q000473:pathology*; D006965:Hyperplasia / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D061965:Matrix Metalloproteinase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects; D009842:Oligopeptides; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015607:Stents / Q000009:adverse effects*; D059005:Topoisomerase II Inhibitors / Q000494:pharmacology; D014162:Transfection
D061965:Matrix Metalloproteinase Inhibitors; D009842:Oligopeptides; D034741:RNA, Small Interfering; D059005:Topoisomerase II Inhibitors; C514703:cholesteryl oligoarginine; D015365:Enoxacin; D002784:Cholesterol; D020780:Matrix Metalloproteinase 9