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Lentivirus-mediated RNAi knockdown of the gap junction protein, Cx43, attenuates the development of vascular restenosis following balloon injury

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 restenosi...

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Autores principales: HAN, XIAO-JIAN, CHEN, MIN, HONG, TAO, ZHU, LING-YU, HE, DAN, FENG, JIU-GENG, JIANG, LI-PING
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356439/
https://www.ncbi.nlm.nih.gov/pubmed/25625334
http://dx.doi.org/10.3892/ijmm.2015.2078
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author HAN, XIAO-JIAN
CHEN, MIN
HONG, TAO
ZHU, LING-YU
HE, DAN
FENG, JIU-GENG
JIANG, LI-PING
author_facet HAN, XIAO-JIAN
CHEN, MIN
HONG, TAO
ZHU, LING-YU
HE, DAN
FENG, JIU-GENG
JIANG, LI-PING
author_sort HAN, XIAO-JIAN
collection PubMed
description 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 reste-nosis. Cx43 may prove to be a novel potential pharmacological target for the prevention of vascular restenosis following PCI.
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spelling pubmed-43564392015-03-18 Lentivirus-mediated RNAi knockdown of the gap junction protein, Cx43, attenuates the development of vascular restenosis following balloon injury HAN, XIAO-JIAN CHEN, MIN HONG, TAO ZHU, LING-YU HE, DAN FENG, JIU-GENG JIANG, LI-PING Int J Mol Med Articles 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 reste-nosis. Cx43 may prove to be a novel potential pharmacological target for the prevention of vascular restenosis following PCI. D.A. Spandidos 2015-04 2015-01-23 /pmc/articles/PMC4356439/ /pubmed/25625334 http://dx.doi.org/10.3892/ijmm.2015.2078 Text en Copyright © 2015, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
HAN, XIAO-JIAN
CHEN, MIN
HONG, TAO
ZHU, LING-YU
HE, DAN
FENG, JIU-GENG
JIANG, LI-PING
Lentivirus-mediated RNAi knockdown of the gap junction protein, Cx43, attenuates the development of vascular restenosis following balloon injury
title Lentivirus-mediated RNAi knockdown of the gap junction protein, Cx43, attenuates the development of vascular restenosis following balloon injury
title_full Lentivirus-mediated RNAi knockdown of the gap junction protein, Cx43, attenuates the development of vascular restenosis following balloon injury
title_fullStr Lentivirus-mediated RNAi knockdown of the gap junction protein, Cx43, attenuates the development of vascular restenosis following balloon injury
title_full_unstemmed Lentivirus-mediated RNAi knockdown of the gap junction protein, Cx43, attenuates the development of vascular restenosis following balloon injury
title_short Lentivirus-mediated RNAi knockdown of the gap junction protein, Cx43, attenuates the development of vascular restenosis following balloon injury
title_sort lentivirus-mediated rnai knockdown of the gap junction protein, cx43, attenuates the development of vascular restenosis following balloon injury
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4356439/
https://www.ncbi.nlm.nih.gov/pubmed/25625334
http://dx.doi.org/10.3892/ijmm.2015.2078
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