Helper-dependent adenovirus-mediated gene transfer of a secreted LDL receptor/transferrin chimeric protein reduces aortic atherosclerosis in LDL receptor-deficient mice (345 views) (PDF public 112 views)
Gene Ther (ISSN: 0969-7128linking), 2019 Jan 30; 26(3-4): 121-130.
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Paper type: Journal Article,
Impact factor: 4.782, 5-year impact factor: 3.67
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Affiliations:
*** IBB - CNR ***
CEINGE-Biotecnologie Avanzate, Napoli, Italy., IRCCS SDN, Napoli, Italy., Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita degli Studi di Napoli Federico II, Napoli, Italy., Dipartimento di Scienze Biomediche Avanzate, Universita degli Studi di Napoli Federico II, Napoli, Italy., Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy., Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", Caserta, Italy., Laboratory of ImmunoViroTherapy, Centre for Drug Research (CDR), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland., CEINGE-Biotecnologie Avanzate, Napoli, Italy. lucio.pastore@unina.it., Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita degli Studi di Napoli Federico II, Napoli, Italy. lucio.pastore@unina.it.,
References:
Not available.
Gene Ther (ISSN: 0969-7128linking), 2019 Jan 30; 26(3-4): 121-130.
Export to BibTeX Export to EndNote
Paper type: Journal Article,
Impact factor: 4.782, 5-year impact factor: 3.67
Url: Not available.
Keywords: Not available.
Affiliations:
*** IBB - CNR ***
CEINGE-Biotecnologie Avanzate, Napoli, Italy., IRCCS SDN, Napoli, Italy., Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita degli Studi di Napoli Federico II, Napoli, Italy., Dipartimento di Scienze Biomediche Avanzate, Universita degli Studi di Napoli Federico II, Napoli, Italy., Istituto di Biostrutture e Bioimmagini, CNR, Napoli, Italy., Department of Environmental, Biological and Pharmaceutical Sciences and Technologies, University of Campania "Luigi Vanvitelli", Caserta, Italy., Laboratory of ImmunoViroTherapy, Centre for Drug Research (CDR), Division of Pharmaceutical Biosciences, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland., CEINGE-Biotecnologie Avanzate, Napoli, Italy. lucio.pastore@unina.it., Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Universita degli Studi di Napoli Federico II, Napoli, Italy. lucio.pastore@unina.it.,
References:
Not available.
Helper-dependent adenovirus-mediated gene transfer of a secreted LDL receptor/transferrin chimeric protein reduces aortic atherosclerosis in LDL receptor-deficient mice
Familial hypercholesterolemia (FH) is a genetic hyperlipidemia characterized by elevated concentrations of plasma LDL cholesterol. Statins are not always effective for the treatment of FH patients; unresponsive patients have poor prognosis and rely on LDL apheresis. In the past, we developed safe and effective gene therapy strategies for the expression of anti-atherogenic proteins using PEGylated helper-dependent adenoviral (HD-Ad) vectors. We recently developed a HD-Ad vector for the expression of the soluble form of the extracellular portion of the human LDL receptor (LDLR) fused with a rabbit transferrin dimer (LDLR-TF). We evaluated the efficacy of the LDLR-TF chimeric protein in CHOLDLA7, a cell line lacking LDLR expression, restoring the ability to uptake LDL. Subsequently, we administered intravenously 1 x 10E13 vp/kg of this vector in LDLR-deficient mice and observed amelioration of lipid profile and reduction of aortic atherosclerosis. Finally, we studied LDL distribution after HD-Ad vector-mediated expression of LDLR-TF in LDLR-deficient mice and found LDL accumulation in liver, and in heart and intestine. These results support the possibility of lowering LDL-C levels and reducing aortic atherosclerosis using a secreted therapeutic transgene; the present strategy potentially can be modified and adapted to non-systemic gene transfer with expression of the secreted chimeric protein in muscle or other tissues. Intramuscular or local administration strategies could improve the safety profile of this strategy and facilitate applicability.
Familial hypercholesterolemia (FH) is a genetic hyperlipidemia characterized by elevated concentrations of plasma LDL cholesterol. Statins are not always effective for the treatment of FH patients; unresponsive patients have poor prognosis and rely on LDL apheresis. In the past, we developed safe and effective gene therapy strategies for the expression of anti-atherogenic proteins using PEGylated helper-dependent adenoviral (HD-Ad) vectors. We recently developed a HD-Ad vector for the expression of the soluble form of the extracellular portion of the human LDL receptor (LDLR) fused with a rabbit transferrin dimer (LDLR-TF). We evaluated the efficacy of the LDLR-TF chimeric protein in CHOLDLA7, a cell line lacking LDLR expression, restoring the ability to uptake LDL. Subsequently, we administered intravenously 1 x 10E13 vp/kg of this vector in LDLR-deficient mice and observed amelioration of lipid profile and reduction of aortic atherosclerosis. Finally, we studied LDL distribution after HD-Ad vector-mediated expression of LDLR-TF in LDLR-deficient mice and found LDL accumulation in liver, and in heart and intestine. These results support the possibility of lowering LDL-C levels and reducing aortic atherosclerosis using a secreted therapeutic transgene; the present strategy potentially can be modified and adapted to non-systemic gene transfer with expression of the secreted chimeric protein in muscle or other tissues. Intramuscular or local administration strategies could improve the safety profile of this strategy and facilitate applicability.
Helper-dependent adenovirus-mediated gene transfer of a secreted LDL receptor/transferrin chimeric protein reduces aortic atherosclerosis in LDL receptor-deficient mice
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Helper-dependent adenovirus-mediated gene transfer of a secreted LDL receptor/transferrin chimeric protein reduces aortic atherosclerosis in LDL receptor-deficient mice
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Sorriento D, Santulli G, Fusco A, Anastasio A, Trimarco B, Iaccarino G
* Intracardiac injection of AdGRK5-NT reduces left ventricular hypertrophy by inhibiting NF-κB-Dependent hypertrophic gene expression (790 views)
Hypertensionhypertension (ISSN: 0194-911x), 2010; 56(4): 696-704.
Impact Factor: 6.908
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Cigliano L, Pugliese CR, Spagnuolo MS, Palumbo R, Abrescia P
* Haptoglobin binds the antiatherogenic protein apolipoprotein e - Impairment of apolipoprotein e stimulation of both lecithin: Cholesterol acyltransferase activity and cholesterol uptake by hepatocytes (566 views)
Febs J (ISSN: 1742-464x), 2009 Nov; 276(21): 6158-6171.
Impact Factor: 3.042
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Coppola G, Fortunato D, Auricchio G, Mainolfi C, Operto FF, Signoriello G, Pascotto A, Salvatore M
* Bone mineral density in children, adolescents, and young adults with epilepsy (714 views)
Epilepsia (ISSN: 1528-1167, 0013-9580), 2009 Sep; 50(9): 2140-2146.
Impact Factor: 4.052
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Garzia L, Andolfo I, Cusanelli E, Marino N, Petrosino G, De Martino D, Esposito V, Galeone A, Navas L, Esposito S, Gargiulo S, Fattet S, Donofrio V, Cinalli G, Brunetti A, Del Vecchio L, Northcott PA, Delattre O, Taylor MD, Iolascon A, Zollo M
* MicroRNA-199b-5p Impairs Cancer Stem Cells through Negative Regulation of HES1 in Medulloblastoma (552 views)
Plosone (ISSN: 1932-6203, 1932-6203electronic, 1932-6203linking), 2009 Mar 24; 4(3): e4998-e4998.
Impact Factor: 4.351
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Sorriento D, Campanile A, Santulli G, Leggiero E, Pastore L, Trimarco B, Iaccarino G
* A new synthetic protein, TAT-RH, inhibits tumor growth through the regulation of NFκB activity (553 views)
Mol Cancermolecular Cancer (ISSN: 1476-4598), 2009; 8: N/D-N/D.
Impact Factor: 4.16
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Vaccaro M, Accardo A, Tesauro D, Mangiapia G, Loef D, Schillen K, Soederman O, Morelli G, Paduan L
* Supramolecular aggregates of amphiphilic gadolinium complexes as blood pool MRI/MRA contrast agents: Physicochemical characterization (546 views)
Langmuir (ISSN: 0743-7463), 2006 Jul 18; 22(15): 6635-6643.
Impact Factor: 3.902
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Cittadini A, Monti MG, Iaccarino G, Di Rella F, Tsichlis PN, Di Gianni A, Strömer H, Sorriento D, Peschle C, Trimarco B, Saccà L, Condorelli G
* Adenoviral gene transfer of Akt enhances myocardial contractility and intracellular calcium handling (2059 views)
Gene Ther (ISSN: 0969-7128, 0969-7128linking), 2006; 13(1): 8-19.
Impact Factor: 4.782
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Colao A, Di Somma C, Cuocolo A, Spinelli L, Acampa W, Spiezia S, Rota F, Savanelli MC, Lombardi G
* Does a gender-related effect of growth hormone (GH) replacement exist on cardiovascular risk factors, cardiac morphology, and performance and atherosclerosis? Results of a two-year open, prospective study in young adult men and women with severe GH deficiency (589 views)
J Clin Endocrinol Metab (ISSN: 0021-972x), 2005 Sep; 90(9): 5146-5155.
Impact Factor: 6.02
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Vicario MLE, Cirillo L, Storto G, Pellegrino T, Ragone N, Fontanella L, Petretta M, Bonaduce D, Cuocolo A
* Influence of risk factors on coronary flow reserve in patients with 1-vessel coronary artery disease (527 views)
J Nucl Med (ISSN: 0161-5505, 1535-5667, 1535-5667electronic), 2005 Sep; 46(9): 1438-1443.
Impact Factor: 4.684
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Cuocolo A, Acampa W, Imbriaco M, De Luca N, Iovino GL, Salvatore M
* The many ways to myocardial perfusion imaging (650 views)
Q J Nucl Med Mol Im (ISSN: 1824-4785, 1824-4478, 1824-4785linking), 2005 Mar; 49(1): 4-18.
Impact Factor: 1.724
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Iaccarino G, Ciccarelli M, Sorriento D, Cipolletta E, Cerullo V, Iovino GL, Paudice A, Elia A, Santulli G, Campanile A, Arcucci O, Pastore L, Salvatore F, Condorelli G, Trimarco B
* AKT participates in endothelial dysfunction in hypertension (648 views)
Circulationcirculation (ISSN: 0009-7322), 2004; 109(21): 2587-2593.
Impact Factor: 12.563
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Portella G, Pacelli R, Libertini S, Cella L, Vecchio G, Salvatore M, Fusco A
* ONYX-015 Enhances Radiation-Induced Death of Human Anaplastic Thyroid Carcinoma Cells (678 views)
J Clin Endocrinol Metab Journal Of Clinical Endocrinology And Metabolism (ISSN: 0021-972x), 2003 Oct 1; 88(10): 5027-5032.
Impact Factor: 5.873
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Pauciullo P, Giannino A, De Michele M, Gentile M, Liguori R, Argiriou A, Carlotto A, Faccenda F, Mancini M, Bond MG, De Simone V, Rubba P
* Increased carotid artery intima-media thickness is associated with a novel mutation of low-density lipoprotein receptor independently of major cardiovascular risk factors (918 views)
Metab Clin Exp (ISSN: 0026-0495, 1532-8600), 2003; 52(11): 1433-1438.
Impact Factor: 2.013
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Zingone A, Seidel J, Aloj L, Caraco C, Vaquero JJ, Jagoda EM, Chou JY, Green MV, Eckelman WC
* Monitoring the correction of glycogen storage disease type 1a in a mouse model using [18F]FDG and a dedicated animal scanner (361 views)
Life Sci (ISSN: 0024-3205), 2002; 71(11): 1293-1301.
Impact Factor: 1.824
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Caraglia M, Tagliaferri P, Correale P, Genua G, Pinto A, Del Vecchio S, Esposito G, Bianco AR
CYTOSINE-ARABINOSIDE INCREASES THE BINDING OF I-125 LABELED EPIDERMAL GROWTH-FACTOR AND I-125 TRANSFERRIN AND ENHANCES THE IN-VITRO TARGETING OF HUMAN TUMOR-CELLS WITH ANTI-(GROWTH FACTOR-RECEPTOR) MAB (389 views)
Cancer Immunol Immunother (ISSN: 0340-7004, 0340-7004linking), 1993 Sep; 37(3): 150-156.
Impact Factor: 1.269
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Caraglia M, Tagliaferri P, Correale P, Genua G, Pinto A, Del Vecchio S, Esposito G, Bianco AR
Cytosine arabinoside increases the binding of 125I-labelled epidermal growth factor and 125I-transferrin and enhances the in vitro targeting of human tumour cells with anti-(growth factor receptor) mAb (389 views)
Cancer Immunol Immunother (ISSN: 0340-7004linking), 1993 Aug; 37 (3 ): 150-156.
Impact Factor: 4.293
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Caraglia M, Correale P, Genua G, Pepe S, Del Vecchio S, Esposito G, Bianco AR, Tagliaferri P
EPIDERMAL GROWTH-FACTOR (EGFR) AND TRANSFERRIN (TRFR) RECEPTOR UP-REGULATION IS INDUCED BY ARABINOSIDE CYTOSINE (ARA-C) ON HUMAN TUMOR-CELLS (314 views)
Cancer Detection And Prevention (ISSN: 0361-090x), 1993; 17(2): 337-338.
Impact Factor: 0.838
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Ferrara LA, Mancini M, Iannuzzi R, Marotta T
Ultrasonographic Evaluation Of Carotid Wall Thickness And Atherosclerosis In Essential Hypertension (385 views)
Fifth European Meeting On Hypertension European Society Of Hypertension Milan, 1991 Oct; N/D: 210-210.
Impact Factor: 0
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Postiglione A, Nappi A, Brunetti A, Soricelli A, Rubba P, Gnasso A, Cammisa M, Frusciante V, Cortese C, Salvatore M
Relative protection from cerebral atherosclerosis of young patients with homozygous familial hypercholesterolemia (577 views)
Atherosclerosis (ISSN: 0021-9150, 1879-1484), 1991 Sep; 90(1): 23-30.
Impact Factor: 2.889
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36 Records (34 excluding Abstracts).
Total impact factor: 138.617 (134.266 excluding Abstracts).
Total 5 year impact factor: 140.601 (136.218 excluding Abstracts).
Total impact factor: 138.617 (134.266 excluding Abstracts).
Total 5 year impact factor: 140.601 (136.218 excluding Abstracts).
345 views. Last view on Tuesday 10 December 2024, 11:28:27
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