Gene delivery of hypoxia-inducible VEGF targeting collagen effectively improves cardiac function after myocardial infarction

Abstract Vascular endothelial growth factor (VEGF) plays important roles in improvement of cardiac function following myocardial infarction (MI). However, the lack of a steerable delivery system of VEGF targeting the infarcted myocardium reduces the therapeutic efficacy and safety. Here, we construc...

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Autores principales:	Jing-Bo Xia, Hai-Yan Wu, Bing-Lin Lai, Li Zheng, Deng-Cheng Zhou, Zao-Shang Chang, Cheng-Zhou Mao, Guang-Hui Liu, Kyu-Sang Park, Hui Zhao, Soo-Ki Kim, Guo-Hua Song, Dong-Qing Cai, Xu-Feng Qi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/37551537bb7b421daf34ddb71884ba40
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spelling	oai:doaj.org-article:37551537bb7b421daf34ddb71884ba402021-12-02T15:05:45ZGene delivery of hypoxia-inducible VEGF targeting collagen effectively improves cardiac function after myocardial infarction10.1038/s41598-017-13547-12045-2322https://doaj.org/article/37551537bb7b421daf34ddb71884ba402017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13547-1https://doaj.org/toc/2045-2322Abstract Vascular endothelial growth factor (VEGF) plays important roles in improvement of cardiac function following myocardial infarction (MI). However, the lack of a steerable delivery system of VEGF targeting the infarcted myocardium reduces the therapeutic efficacy and safety. Here, we constructed a series of lentiviral vector systems which could express a fusion protein consisted of a collagen-binding domain (CBD) and hVEGF (CBDhVEGF), under the control of 5HRE-hCMVmp (5HRE), the hypoxia-inducible promoter consists of five copies of the hypoxia-responsive element (HRE) and a human cytomegalovirus minimal promoter (hCMVmp). We demonstrated that 5HRE has the comparable ability to strongly drive CBDhVEGF under hypoxic condition as the ubiquitous CMV promoter, but it can hardly drive target gene under normoxic condition. 5HRE-drived CBDhVEGF specifically bound to type I collagen and significantly promoted the viability of HUVEC cells. Moreover, after injection of lentivirus into heart of mouse with MI, CBDhVEGF was mainly retained in infarcted myocardium where containing rich collagen and significantly improved angiogenesis and cardiac function when compared with hVEGF. Moreover, CBDhVEGF mediated by lentivirus has little leakage from infarcted zone into blood than hVEGF. Taken together, our results indicate that 5HRE-CBDhVEGF lentiviral vector system could improve cardiac function in the collagen-targeting and hypoxia-inducible manners.Jing-Bo XiaHai-Yan WuBing-Lin LaiLi ZhengDeng-Cheng ZhouZao-Shang ChangCheng-Zhou MaoGuang-Hui LiuKyu-Sang ParkHui ZhaoSoo-Ki KimGuo-Hua SongDong-Qing CaiXu-Feng QiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jing-Bo Xia Hai-Yan Wu Bing-Lin Lai Li Zheng Deng-Cheng Zhou Zao-Shang Chang Cheng-Zhou Mao Guang-Hui Liu Kyu-Sang Park Hui Zhao Soo-Ki Kim Guo-Hua Song Dong-Qing Cai Xu-Feng Qi Gene delivery of hypoxia-inducible VEGF targeting collagen effectively improves cardiac function after myocardial infarction
description	Abstract Vascular endothelial growth factor (VEGF) plays important roles in improvement of cardiac function following myocardial infarction (MI). However, the lack of a steerable delivery system of VEGF targeting the infarcted myocardium reduces the therapeutic efficacy and safety. Here, we constructed a series of lentiviral vector systems which could express a fusion protein consisted of a collagen-binding domain (CBD) and hVEGF (CBDhVEGF), under the control of 5HRE-hCMVmp (5HRE), the hypoxia-inducible promoter consists of five copies of the hypoxia-responsive element (HRE) and a human cytomegalovirus minimal promoter (hCMVmp). We demonstrated that 5HRE has the comparable ability to strongly drive CBDhVEGF under hypoxic condition as the ubiquitous CMV promoter, but it can hardly drive target gene under normoxic condition. 5HRE-drived CBDhVEGF specifically bound to type I collagen and significantly promoted the viability of HUVEC cells. Moreover, after injection of lentivirus into heart of mouse with MI, CBDhVEGF was mainly retained in infarcted myocardium where containing rich collagen and significantly improved angiogenesis and cardiac function when compared with hVEGF. Moreover, CBDhVEGF mediated by lentivirus has little leakage from infarcted zone into blood than hVEGF. Taken together, our results indicate that 5HRE-CBDhVEGF lentiviral vector system could improve cardiac function in the collagen-targeting and hypoxia-inducible manners.
format	article
author	Jing-Bo Xia Hai-Yan Wu Bing-Lin Lai Li Zheng Deng-Cheng Zhou Zao-Shang Chang Cheng-Zhou Mao Guang-Hui Liu Kyu-Sang Park Hui Zhao Soo-Ki Kim Guo-Hua Song Dong-Qing Cai Xu-Feng Qi
author_facet	Jing-Bo Xia Hai-Yan Wu Bing-Lin Lai Li Zheng Deng-Cheng Zhou Zao-Shang Chang Cheng-Zhou Mao Guang-Hui Liu Kyu-Sang Park Hui Zhao Soo-Ki Kim Guo-Hua Song Dong-Qing Cai Xu-Feng Qi
author_sort	Jing-Bo Xia
title	Gene delivery of hypoxia-inducible VEGF targeting collagen effectively improves cardiac function after myocardial infarction
title_short	Gene delivery of hypoxia-inducible VEGF targeting collagen effectively improves cardiac function after myocardial infarction
title_full	Gene delivery of hypoxia-inducible VEGF targeting collagen effectively improves cardiac function after myocardial infarction
title_fullStr	Gene delivery of hypoxia-inducible VEGF targeting collagen effectively improves cardiac function after myocardial infarction
title_full_unstemmed	Gene delivery of hypoxia-inducible VEGF targeting collagen effectively improves cardiac function after myocardial infarction
title_sort	gene delivery of hypoxia-inducible vegf targeting collagen effectively improves cardiac function after myocardial infarction
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/37551537bb7b421daf34ddb71884ba40
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Gene delivery of hypoxia-inducible VEGF targeting collagen effectively improves cardiac function after myocardial infarction

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