title: A nanoformulation containing a scFv reactive to electronegative LDL inhibits atherosclerosis in LDL receptor knockout mice.
abstract: 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.
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Marcela Frota
authors.initials: MF
authors.lastname: Cavalcante
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Soraya Megumi
authors.initials: SM
authors.lastname: Kazuma
authors.affiliation: Department of Organic Chemistry, Chemistry Institute, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Eduardo André
authors.initials: EA
authors.lastname: Bender
authors.affiliation: Department of Organic Chemistry, Chemistry Institute, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Márcia Duarte
authors.initials: MD
authors.lastname: Adorne
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Mayara
authors.initials: M
authors.lastname: Ullian
authors.affiliation: LIM5, Department of Pathology, Medicine School, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Mariana Matera
authors.initials: MM
authors.lastname: Veras
authors.affiliation: LIM5, Department of Pathology, Medicine School, University of Sao Paulo, Sao Paulo, SP, Brazil.
authors.forename: Paulo Hilário Nascimento
authors.initials: PH
authors.lastname: Saldiva
authors.affiliation: Molecular Immunology Laboratory, Department of Cell Biology, University of Brasilia, Brasilia, Distrito Federal, Brazil.
authors.forename: Andrea Queiroz
authors.initials: AQ
authors.lastname: Maranhão
authors.affiliation: Department of Production and Control of Medicines, Faculty of Pharmacy, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Silvia Stanisçuaski
authors.initials: SS
authors.lastname: Guterres
authors.affiliation: Department of Organic Chemistry, Chemistry Institute, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Adriana Raffin
authors.initials: AR
authors.lastname: Pohlmann
authors.affiliation: Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, SP, Brazil. Electronic address: dspabdalla@gmail.com.
authors.forename: Dulcineia Saes Parra
authors.initials: DS
authors.lastname: Abdalla
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000517:prevention & control*; D002460:Cell Line; D008077:Lipoproteins, LDL / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000235:genetics / Q000502:physiology*; D057127:Single-Chain Antibodies / Q000276:immunology*
chemical_list: D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D057127:Single-Chain Antibodies
keywords: Atherosclerosis; Electronegative LDL; Foam cell; Macrophage; Nanocapsules; Single chain fragment variable