Therapeutic Effect of Akt1 siRNA Nanoparticle Eluting Coronary Stent on Suppression of Post-Angioplasty Restenosis.
For effective treatment of restenosis, therapeutic genes are delivered locally from a coated stent at the site of injury, leading to inhibition of smooth muscle proliferation and neo-intimal hyperplasia while promoting re-endothelialization. In a previous study, we delivered Akt1 siRNA nanoparticles (ASNs) from a hyaluronic acid (HA)-coated stent surface to specifically suppress the pro-proliferative Akt1 protein in smooth muscle cells (SMCs). In the present study, therapeutic efficacy was investigated in a rabbit restenosis model after percutaneous implantation of an ASN-immobilized stent in a rabbit iliac artery. Quantitative and qualitative analyses of in-stent restenosis were investigated in an in vivo animal model by micro-CT imaging and SEM observation, respectively. Proliferation status and neo-intima formation of the vascular tissues located near ASN-immobilized stents were analyzed by immunohistochemical staining using anti-Akt1 and anti-Ki67 antibodies and histological analyses, such as hematoxylin and eosin staining and Verhoeff's elastic stain. Re-endothelialization after implantation of an ASN-immobilized stent was also analyzed via immunohistochemistry using an anti-CD31 antibody. To elucidate the molecular mechanism related to reducing SMC proliferation and subsequent inhibition of in-stent restenosis in vivo, protein and mRNA expression of Akt1 and downstream signaling proteins were analyzed after isolating SMC-rich samples from the treated vasculature. The implanted Akt1 siRNA-eluting stent efficiently mitigated in-stent restenosis without any side effects and can be considered a successful substitute to current drug-eluting stents.
Hui-Lian
HL
Che
In-Hi
IH
Bae
Kyung Seob
KS
Lim
In Taek
IT
Song
Haeshin
H
Lee
Duhwan
D
Lee
Won Jong
WJ
Kim
Myung-Ho
MH
Jeong
Youngkeun
Y
Ahn
D017130:Angioplasty; D000818:Animals; D023903:Coronary Restenosis / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D023921:Coronary Stenosis / Q000473:pathology / Q000601:surgery; D003331:Coronary Vessels / Q000473:pathology / Q000601:surgery; D004337:Drug Carriers / Q000737:chemistry; D054855:Drug-Eluting Stents; D006820:Hyaluronic Acid; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics* / Q000627:therapeutic use*; D011817:Rabbits; D055114:X-Ray Microtomography
D004337:Drug Carriers; D034741:RNA, Small Interfering; D006820:Hyaluronic Acid; D051057:Proto-Oncogene Proteins c-akt