title: Gene delivery of soluble vascular endothelial growth factor receptor-1 (sFlt-1) inhibits intra-plaque angiogenesis and suppresses development of atherosclerotic plaque.
abstract: 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.
authors.affiliation: Department of Cardiovascular Disease, Second Affiliated Hospital, Nanchang University, Jiangxi Province, People's Republic of China.
authors.forename: Yaosheng
authors.initials: Y
authors.lastname: Wang
authors.forename: Yihua
authors.initials: Y
authors.lastname: Zhou
authors.forename: Lipeng
authors.initials: L
authors.lastname: He
authors.forename: Kui
authors.initials: K
authors.lastname: Hong
authors.forename: Hai
authors.initials: H
authors.lastname: Su
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Wu
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Wu
authors.forename: Mihan
authors.initials: M
authors.lastname: Han
authors.forename: Xiaoshu
authors.initials: X
authors.lastname: Cheng
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000502:physiology; D015870:Gene Expression; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D058226:Plaque, Atherosclerotic / Q000473:pathology* / Q000628:therapy*; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics* / Q000378:metabolism*
chemical_list: D011994:Recombinant Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D040281:Vascular Endothelial Growth Factor Receptor-1
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