期刊
SMALL
卷 18, 期 13, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202105915
关键词
apoA-I; atherosclerosis models; cardiovascular diseases; cholesterol efflux; microRNAs; nanodiscs; recombinant; reconstituted high-density lipoproteins (rHDL)
类别
资金
- Ministerio De Ciencia e Innovacion
- Proyectos De Generacion De Conocimiento 2021 [PID2021-127056OB-I00]
- Fundacion Biofisica Bizkaia
- Programa de especializacion de Personal Investigador Doctor en la UPV/EHU (2019) 2019-2020
- grant Programa Investigador en Formacion (2017-2018), Gobierno Vasco
- grant Programa Investigador en Formacion (2019-2020), Gobierno Vasco
A therapeutic strategy based on apoA-I nanoparticles has been developed to improve the treatment of atherosclerosis. The strategy involves a two-step administration to induce gene overexpression and promote cholesterol efflux. Experimental results indicate that this approach can efficiently target atherosclerotic lesions and improve prognosis.
Cardiovascular disease, the leading cause of mortality worldwide, is primarily caused by atherosclerosis, which is characterized by lipid and inflammatory cell accumulation in blood vessels and carotid intima thickening. Although disease management has improved significantly, new therapeutic strategies focused on accelerating atherosclerosis regression must be developed. Atherosclerosis models mimicking in vivo-like conditions provide essential information for research and new advances toward clinical application. New nanotechnology-based therapeutic opportunities have emerged with apoA-I nanoparticles (recombinant/reconstituted high-density lipoproteins, rHDL) as ideal carriers to deliver molecules and the discovery that microRNAs participate in atherosclerosis establishment and progression. Here, a therapeutic strategy to improve cholesterol efflux is developed based on a two-step administration of rHDL consisting of a first dose of antagomiR-33a-loaded rHDLs to induce adenosine triphosphate-binding cassette transporters A1 overexpression, followed by a second dose of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine rHDLs, which efficiently remove cholesterol from foam cells. A triple-cell 2D-atheroma plaque model reflecting the cellular complexity of atherosclerosis is used to improve efficiency of the nanoparticles in promoting cholesterol efflux. The results show that sequential administration of rHDL potentiates cholesterol efflux indicating that this approach may be used in vivo to more efficiently target atherosclerotic lesions and improve prognosis of the disease.
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