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http://purl.uniprot.org/citations/28504688http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28504688http://www.w3.org/2000/01/rdf-schema#comment"Studying the role of a particular gene in atherosclerosis typically requires a time-consuming and often difficult process of generating double knockouts or transgenics on ApoE-/- or LDL receptor (LDLR)-/- background. Recently, it was reported that adeno-associated-virus-8 (AAV8)-mediated overexpression of PCSK9 (AAV8-PCSK9) rapidly induced hyperlipidemia. However, using this method in C57BL6 wild-type (C57) mice, it took ~3 months to develop atherosclerosis. Our partial carotid ligation model is used to rapidly develop atherosclerosis by inducing disturbed flow in the left common carotid artery within 2 weeks in ApoE-/- or LDLR-/- mice. Here, we combined these two approaches to develop an accelerated model of atherosclerosis in C57 mice. C57 mice were injected with AAV9-PCSK9 or AAV9-luciferase (control) and high-fat diet was initiated. A week later, partial ligation was performed. Compared to the control, AAV-PCSK9 led to elevated serum PCSK9, hypercholesterolemia, and rapid atherosclerosis development within 3 weeks as determined by gross plaque imaging, and staining with Oil-Red-O, Movat's pentachrome, and CD45 antibody. These plaque lesions were comparable to the atherosclerotic lesions that have been previously observed in ApoE-/- or LDLR-/- mice that were subjected to partial carotid ligation and high-fat diet. Next, we tested whether our method can be utilized to rapidly determine the role of a particular gene in atherosclerosis. Using eNOS-/- and NOX1-/y mice on C57 background, we found that the eNOS-/- mice developed more advanced lesions, while the NOX1-/y mice developed less atherosclerotic lesions as compared to the C57 controls. These results are consistent with the previous findings using double knockouts (eNOS-/-_ApoE-/- and NOX1-/y_ApoE-/-). AAV9-PCSK9 injection followed by partial carotid ligation is an effective and time-saving approach to rapidly induce atherosclerosis. This accelerated model is well-suited to quickly determine the role of gene(s) interest without generating double or triple knockouts."xsd:string
http://purl.uniprot.org/citations/28504688http://purl.org/dc/terms/identifier"doi:10.1038/labinvest.2017.47"xsd:string
http://purl.uniprot.org/citations/28504688http://purl.uniprot.org/core/author"Kumar S."xsd:string
http://purl.uniprot.org/citations/28504688http://purl.uniprot.org/core/author"Jo H."xsd:string
http://purl.uniprot.org/citations/28504688http://purl.uniprot.org/core/author"Kang D.W."xsd:string
http://purl.uniprot.org/citations/28504688http://purl.uniprot.org/core/author"Rezvan A."xsd:string
http://purl.uniprot.org/citations/28504688http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/28504688http://purl.uniprot.org/core/name"Lab Invest"xsd:string
http://purl.uniprot.org/citations/28504688http://purl.uniprot.org/core/pages"935-945"xsd:string
http://purl.uniprot.org/citations/28504688http://purl.uniprot.org/core/title"Accelerated atherosclerosis development in C57Bl6 mice by overexpressing AAV-mediated PCSK9 and partial carotid ligation."xsd:string
http://purl.uniprot.org/citations/28504688http://purl.uniprot.org/core/volume"97"xsd:string
http://purl.uniprot.org/citations/28504688http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/28504688
http://purl.uniprot.org/citations/28504688http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/28504688
http://purl.uniprot.org/uniprot/#_E9Q9X4-mappedCitation-28504688http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28504688
http://purl.uniprot.org/uniprot/#_E0CYB0-mappedCitation-28504688http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28504688
http://purl.uniprot.org/uniprot/#_A0A1B0GX15-mappedCitation-28504688http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28504688
http://purl.uniprot.org/uniprot/#_A0A0R4J1X7-mappedCitation-28504688http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28504688
http://purl.uniprot.org/uniprot/#_G3UWN5-mappedCitation-28504688http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28504688
http://purl.uniprot.org/uniprot/#_G3UWW2-mappedCitation-28504688http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28504688
http://purl.uniprot.org/uniprot/#_G3UZM8-mappedCitation-28504688http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28504688
http://purl.uniprot.org/uniprot/#_Q4FK40-mappedCitation-28504688http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28504688
http://purl.uniprot.org/uniprot/#_Q3TX45-mappedCitation-28504688http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28504688
http://purl.uniprot.org/uniprot/#_Q3TXU4-mappedCitation-28504688http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28504688
http://purl.uniprot.org/uniprot/#_P08226-mappedCitation-28504688http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/28504688