A nanoformulation containing a scFv reactive to electronegative LDL inhibits atherosclerosis in LDL receptor knockout mice

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art_CAVALCANTE_A_nanoformulation_containing_a_scFv_reactive_to_electronegative_2016.PDF (1.32 MB)
Citações na Scopus
12
Tipo de produção
article
Data de publicação
2016
Editora
ELSEVIER SCIENCE BV
DOI
Indexadores
Scopus
Web of Science
PubMed
Título da Revista
ISSN da Revista
Título do Volume
Autores
CAVALCANTE, Marcela Frota
KAZUMA, Soraya Megumi
BENDER, Eduardo Andre
ADORNE, Marcia Duarte
ULLIAN, Mayara
MARANHAO, Andrea Queiroz
GUTERRES, Silvia Staniscuaski
POHLMANN, Adriana Raffin
Autor de Grupo de pesquisa
Editores
Coordenadores
Organizadores
Citação
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, v.107, p.120-129, 2016
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Atherosclerosis is a chronic inflammatory disease responsible for the majority of cases of myocardial infarction and ischemic stroke. The electronegative low-density lipoprotein, a modified subfraction of native LDL, is pro-inflammatory and plays an important role in atherogenesis. To investigate the effects of a nanoformulation (scFv anti-LDL(-)-MCMN-Zn) containing a scFv reactive to LDL(-) on the inhibition of atherosclerosis, its toxicity was evaluated in vitro and in vivo and further it was also administered weekly to LDL receptor knockout mice. The scFv anti-LDL(-)-MCMN-Zn nanoformulation did not induce cell death in RAW 264.7 macrophages and HUVECs. The 5 mg/kg dose of scFv anti-LDL(-)-MCMN-Zn did not cause any typical signs of toxicity and it was chosen for the evaluation of its atheroprotective effect in LdIr(-/-) mice. This nanoformulation significantly decreased the atherosclerotic lesion area at the aortic sinus, compared with that in untreated mice. In addition, the Il1b mRNA expression and CD14 protein expression were downregulated in the atherosclerotic lesions at the aortic arch of LdIr(-/-) mice treated with scFv anti-LDL(-)-MCMN-Zn. Thus, the scFv anti-LDL(-)-MCMN-Zn nanoformulation inhibited the progression of atherosclerotic lesions, indicating its potential use in a future therapeutic strategy for atherosclerosis.
Palavras-chave
Atherosclerosis, Nanocapsules, Single chain fragment variable, Electronegative LDL, Macrophage, Foam cell
URI
https://observatorio.fm.usp.br/handle/OPI/17186
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Coleções
Artigos e Materiais de Revistas Científicas - FM/MPT
Artigos e Materiais de Revistas Científicas - HC/InCor
Artigos e Materiais de Revistas Científicas - LIM/05
Artigos e Materiais de Revistas Científicas - ODS/03