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Journal article
APOA-1Milano muteins, orally delivered via genetically modified rice, show anti-atherogenic and anti-inflammatory properties in vitro and in Apoe(-/-) atherosclerotic mice
International journal of cardiology, v 271, pp 233-239
15 Nov 2018
PMID: 29907443
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Atherosclerosis is a slowly progressing, chronic multifactorial disease characterized by the accumulation of lipids, inflammatory cells, and fibrous tissue that drives to the formation of asymmetric focal thickenings in the tunica intima of large and mid-sized arteries. Despite the high therapeutic potential of ApoA-1 proteins, the purification and delivery into the disordered organisms of these drugs is still limited by low efficiency in these processes.
Methods and results: We report here a novel production and delivery system of anti-atherogenic APOA-1Milano muteins (APOA-1M) by means of genetically modified rice plants. APOA-1M, delivered as protein extracts from transgenic rice seeds, significantly reduced macrophage activation and foam cell formation in vitro in oxLDL-loaded THP-1 model. The APOA-1M delivery method and therapeutic efficacy was tested in healthy mice and in Apoe(-/-) mice fed with high cholesterol diet(Western Diet, WD). APOA-1Mrice milk significantly reduced atherosclerotic plaque size and lipids composition in aortic sinus and aortic arch of WD-fed Apoe(-/-) mice as compared to wild type rice milk-treated, WD-fed Apoe(-/-) mice. APOA-1M rice milk also significantly reduced macrophage number in liver of WD-fed Apoe(-/-) mice as compared to WT rice milk treated mice.
Translational impact: The delivery of therapeutic APOA-1M full length proteins via oral administration of rice seeds protein extracts (the 'rice milk') to the disordered organism, without any need of purification, might overcome the main APOA1-based therapies' limitations and improve the use of this molecules as therapeutic agents for cardiovascular patients. (c) 2018 The Authors. Published by Elsevier B.V.
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Details
- Title
- APOA-1Milano muteins, orally delivered via genetically modified rice, show anti-atherogenic and anti-inflammatory properties in vitro and in Apoe(-/-) atherosclerotic mice
- Creators
- Gabriele Romano - Drexel University, Pharmacology and PhysiologySerena Reggi - Plantechno (Italy)Barbara Kutryb-Zajac - University of GdańskAmanda Facoetti - University of Milano-BicoccaElisa Chisci - University of Milano-BicoccaMariateresa Pettinato - University of Milano-BicoccaMaria Rita Giuffre - University of Milano-BicoccaFederica Vecchio - Azienda Socio Sanitaria Territoriale LarianaSilvia Leoni - University of Milano-BicoccaMarco De Giorgi - University of Milano-BicoccaFederica Avezza - University of Milano-BicoccaMassimiliano Cadamuro - University of Milano-BicoccaLuca Crippa - University of Milano-BicoccaBiagio Eugenio Leone - University of Milano-BicoccaMarialuisa Lavitrano - University of Milano-BicoccaIlaria Rivolta - University of Milano-BicoccaDonatella Barisani - University of Milano-BicoccaRyszard Tomasz Smolenski - Gdańsk Medical UniversityRoberto Giovannoni - University of Milano-Bicocca
- Publication Details
- International journal of cardiology, v 271, pp 233-239
- Publisher
- Elsevier
- Number of pages
- 7
- Grant note
- 2015-ATE-0277; 2016-ATE-0083 / University of Milano-Bicocca
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000444611600062
- Scopus ID
- 2-s2.0-85045700302
- Other Identifier
- 991021965770504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Cardiac & Cardiovascular Systems