caa a22 4500 445354860 CHVBK 20180317142856.0 cr unu---uuuuu 170323e20110601xx s 000 0 eng 10.1007/s10238-010-0112-7 doi (NATIONALLICENCE)springer-10.1007/s10238-010-0112-7 Gene delivery of soluble vascular endothelial growth factor receptor-1 (sFlt-1) inhibits intra-plaque angiogenesis and suppresses development of atherosclerotic plaque [Elektronische Daten] [Yaosheng Wang, Yihua Zhou, Lipeng He, Kui Hong, Hai Su, Yanqing Wu, Qinghua Wu, Mihan Han, Xiaoshu Cheng] Intra-plaque angiogenesis plays an important role in the development of atherosclerotic plaque. Vascular endothelial growth factor (VEGF) is a major initiating factor in this pathologic progress. One selective and specific inhibitor of VEGF is soluble VEGF receptor-1 (sFlt-1). The anti-angiogenic utilization of sFlt-1 in treatment of atherosclerotic plaque has not been fully confirmed yet. Our study was designed to construct eukaryotic expression recombinant pEGFP-N1-sFlt-1, evaluate sFlt-1 recombinant's effects on endothelial cells proliferation and tube formation in vitro, and investigate effects of local high-expressed sFlt-1 on atherosclerotic plaque in vivo. Rabbit models of atherosclerotic plaque were established by high-lipid diet combined with injury induced by balloon catheter on iliac artery intima. Animals were divided into four groups randomly: control group (C), atherosclerotic plaque group (AP), atherosclerotic plaque with blank vector pEGFP-N1 transfection group (APV), and atherosclerotic plaque with pEGFP-N1-sFlt-1 transfection group (APsFlt-1). The local expression of sFlt-1 protein in target artery was detected by western blotting. The plaque area (PA), plaque circumference (PC), and maximum plaque thickness (MPT) were measured via HE staining. Degree of intra-plaque angiogenesis was evaluated by CD34+ cells immunohistochemistry. As results, we observed that pEGFP-N1-sFlt-1 transfection suppressed the HUVECs proliferation and ability of tube formation, against the effect of VEGF. We obtained higher local expression of sFlt-1 protein in Group APsFlt-1 than that in other groups (P<0.05). PA, PC, and MPT of plaque in group APsFlt-1 were significantly decreased when compared with other groups (P<0.05). Amount of annulations surrounded by CD34-positive cells was significantly decreased in pEGFP-N1-sFlt-1 transfection group, which represented decreased level of intra-plaque neovessels formation. The present study confirmed that local gene delivery of sFlt-1 can suppress plaque formation, as one of possible mechanisms, via inhibitive effect on intra atherosclerotic plaque angiogenesis, which hints at the clinical utility of sFlt-1 in atherosclerosis therapy. Springer-Verlag, 2010 Atherosclerotic plaque nationallicence Angiogenesis nationallicence Soluble vascular endothelial growth factor receptor-1 nationallicence Vascular endothelial growth factor nationallicence Wang Yaosheng Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut Zhou Yihua Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut He Lipeng Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut Hong Kui Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut Su Hai Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut Wu Yanqing Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut Wu Qinghua Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut Han Mihan Faculty of Medicine, University of Toronto, M5S 1A8, Toronto, ON, Canada aut Cheng Xiaoshu Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut Clinical and Experimental Medicine Springer Milan 11/2(2011-06-01), 113-121 1591-8890 11:2<113 2011 11 10238 https://doi.org/10.1007/s10238-010-0112-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10238-010-0112-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Wang Yaosheng Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut NATIONALLICENCE 700 1- Zhou Yihua Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut NATIONALLICENCE 700 1- He Lipeng Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut NATIONALLICENCE 700 1- Hong Kui Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut NATIONALLICENCE 700 1- Su Hai Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut NATIONALLICENCE 700 1- Wu Yanqing Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut NATIONALLICENCE 700 1- Wu Qinghua Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut NATIONALLICENCE 700 1- Han Mihan Faculty of Medicine, University of Toronto, M5S 1A8, Toronto, ON, Canada aut NATIONALLICENCE 700 1- Cheng Xiaoshu Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, 1 MinDe Street, 330006, Nanchang, Jiangxi Province, People's Republic of China aut NATIONALLICENCE 773 0- Clinical and Experimental Medicine Springer Milan 11/2(2011-06-01), 113-121 1591-8890 11:2<113 2011 11 10238 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer