title: Lentivirus-mediated RNAi knockdown of the gap junction protein, Cx43, attenuates the development of vascular restenosis following balloon injury.
abstract: Percutaneous coronary intervention [PCI or percutaneous transluminal coronary angioplasty (PTCA)] has been developed into a mature interventional treatment for atherosclerotic cardiovascular disease. However, the long-term therapeutic effect is compromised by the high incidence of vascular restenosis following angioplasty, and the underlying mechanisms of vascular restenosis have not yet been fully elucidated. In the present study, we investigated the role of the gap junction (GJ) protein, connexin 43 (Cx43), in the development of vascular restenosis. To establish vascular restenosis, rat carotid arteries were subjected to balloon angioplasty injury. At 0, 7, 14 and 2 days following balloon injury, the arteries were removed, and the intimal/medial area of the vessels was measured to evaluate the degree of restenosis. We found that the intimal area gradually increased following balloon injury. Intimal hyperplasia and restenosis were particularly evident at 14 and 28 days after injury. In addition, the mRNA and protein expression of Cx43 was temporarily decreased at 7 days, and subsequently increased at 14 and 28 days following balloon injury, as shown by RT-PCR and western blot analysis. To determine the involvement of Cx43 in vascular restenosis, the lentivirus vector expressing shRNA targeting Cx43, Cx43-RNAi-LV, was used to silence Cx43 in the rat carotid arteries. The knockdown of Cx43 effectively attenuated the development of intimal hyperplasia and vascular restenosis following balloon injury. Thus, our data indicate the vital role of the GJ protein, Cx43, in the development of vascular restenosis, and provide new insight into the pathogenesis of vascular restenosis. Cx43 may prove to be a novel potential pharmacological target for the prevention of vascular restenosis following PCI.
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Han
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Tao
authors.initials: T
authors.lastname: Hong
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Ling-Yu
authors.initials: LY
authors.lastname: Zhu
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Jiu-Geng
authors.initials: JG
authors.lastname: Feng
authors.affiliation: Department of Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Jiang
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D018031:Connexin 43 / Q000235:genetics* / Q000378:metabolism; D023903:Coronary Restenosis / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics*; D016086:Lentivirus / Q000235:genetics*; D008297:Male; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology
chemical_list: D018031:Connexin 43; D012333:RNA, Messenger