A nanoformulation containing a scFv reactive to electronegative LDL inhibits atherosclerosis in LDL receptor knockout mice
| Autor: | Andrea Queiroz Maranhão, Soraya Megumi Kazuma, Marcela Frota Cavalcante, Dulcinéia Saes Parra Abdalla, Mariana Matera Veras, Mayara Ullian, Márcia Duarte Adorne, Silvia Stanisçuaski Guterres, Eduardo André Bender, Paulo Hilário Nascimento Saldiva, Adriana Raffin Pohlmann |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male Programmed cell death CD14 NANOTECNOLOGIA Pharmaceutical Science chemical and pharmacologic phenomena 030204 cardiovascular system & hematology Pharmacology Cell Line 03 medical and health sciences Mice 0302 clinical medicine In vivo Animals Foam cell Mice Knockout Chemistry General Medicine respiratory system Atherosclerosis Lipoproteins LDL Mice Inbred C57BL 030104 developmental biology Receptors LDL LDL receptor Immunology Toxicity Knockout mouse lipids (amino acids peptides and proteins) Biotechnology Lipoprotein Single-Chain Antibodies |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1873-3441 |
| Popis: | 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 5mg/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 Ldlr(-/-) 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 Ldlr(-/-) 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. |
| Databáze: | OpenAIRE |
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