title: Prevention of neointimal hyperplasia in balloon-injured rat carotid artery via small interference RNA mediated downregulation of osteopontin gene.
abstract: The aim of the present study was to take osteopontin (OPN) as molecular target to study its effects on injured intima model of carotid artery in rat using perivascular transfer of OPN-small interference RNA (siRNA). OPN mRNA in cultured VSMCs was quantified by real-time RT-PCR, and OPN-siRNA-002 was determined as the most sensitive sequence and used as transfected siRNA in the subsequent animal experiments. We established rat carotid arterial intima-injured model with balloon-injured method, and then perivascularly transfected OPN-siRNA-002 to study the role of OPN-siRNA in regulating several related genes including proliferating cell nuclear antigen (PCNA), transforming growth factor β1(TGF-β1), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-14 (MMP-14), as well as its role in neointimal formation. OPN mRNA and protein decreased about 50 % with corresponding decrease in intima thickness after transfecting with specific OPN-siRNA-002 compared with Pluronic control group and OPN-SCR-siRNA group on each time point (n = 6, p < 0.001), and this inhibiting effects persisted up to 14 days after balloon injury. PCNA, TGF-β1, MMP-2, and MMP-14 mRNA and protein correlated directly with the respective levels of OPN, suggesting its functions via regulating these downstream factors (n = 6, p < 0.001). OPN may be a potential target gene in reducing the risk for arterial restenosis after vascular intervention.
authors: Department of Cardiology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, China.
authors: Jian
authors: J
authors: Xu
authors: Yingxian
authors: Y
authors: Sun
authors: Tairan
authors: T
authors: Wang
authors: Guinan
authors: G
authors: Liu
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000209:etiology / Q000473:pathology*; D017536:Carotid Artery, Common / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D015536:Down-Regulation; D015870:Gene Expression; D006965:Hyperplasia / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D058426:Neointima / Q000473:pathology*; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D011183:Postoperative Complications / Q000209:etiology / Q000473:pathology / Q000517:prevention & control; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D057772:Vascular System Injuries / Q000209:etiology / Q000473:pathology
chemical_list: D034741:RNA, Small Interfering; C506897:Spp1 protein, rat; D053495:Osteopontin; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D053511:Matrix Metalloproteinase 14