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  • Ovid Technologies (Wolters Kluwer Health)  (2)
  • 2010-2014  (2)
  • 1
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 30, No. 5 ( 2010-05), p. 946-952
    Abstract: Objective— Atherosclerosis is an inflammatory disease. Autoimmune responses to low-density lipoproteins (LDL) contribute to its progression, whereas immunization with LDL may induce atheroprotective or proatherogenic responses. The objective of this study was to develop an atheroprotective vaccine by targeting a peptide of the LDL protein constituent apolipoprotein B-100 (apoB-100) to the nasal mucosa to induce a protective mucosal immune response. Methods and Results— A peptide comprising amino acids 3136 to 3155 of apoB-100 (p210) was fused to the B subunit of cholera toxin (CTB), which binds to a ganglioside on mucosal epithelia. The effect of nasal administration of the p210-CTB fusion protein on atherogenesis was compared with that of an ovalbumin peptide fused to CTB and with untreated controls. Immunization with p210-CTB for 12 weeks caused a 35% reduction in aortic lesion size in Apoe −/− mice. This effect was accompanied by induction of regulatory T cells that markedly suppressed effector T cells rechallenged with apoB-100 and increased numbers of interleukin (IL)-10 + CD4 + T cells. Furthermore, a peptide-specific antibody response was observed. Atheroprotection was also documented in apoe −/− mice lacking functional transforming growth factor-β receptors on T cells. Conclusion— Nasal administration of an apoB-100 peptide fused to CTB attenuates atherosclerosis and induces regulatory Tr1 cells that inhibit T effector responses to apoB-100.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2010
    detail.hit.zdb_id: 1494427-3
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  • 2
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2013
    In:  Arteriosclerosis, Thrombosis, and Vascular Biology Vol. 33, No. suppl_1 ( 2013-05)
    In: Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. suppl_1 ( 2013-05)
    Abstract: It is well established that patients with Rheumatoid Arthritis (RA) have a higher risk of developing coronary artery disease (CAD). However, it is unclear how the inflammatory process affects atherosclerosis and what specific factors are involved. In this study, we investigated the effect of the pro-atherogenic factor hyperlipidaemia on arthritis incidence and severity. Simultaneously, we have investigated the mutation of the neutrophil cytosolic factor 1 (Ncf-1), a known genetic factor that promotes arthritis susceptibility, and MHCII H-2q on atherosclerosis development. Results We observed that diet-induced hyperlipidaemia prior to induction of collagen induced arthritis (CIA) protected mice against the disease while genetically hyperlipidemic without the use of diet, Ldlr-/- x human ApoB100 transgenic (Ldlr-/-hApoBtg), were equally susceptible to CIA compared to their heterozygous littermates. Next, we investigated Ncf-1 mutation on Ldlr-/-hApoBtg mice. Surprisingly, despite the increased inflammatory/arthritic phenotype induced by Ncf-1 mutation, no difference in the atherosclerotic lesion size was observed. Conclusions Our data shows that hyperlipidaemia-induced by diet have substantial effects on arthritis susceptibility, which in turn differs from hyperlipidaemia acquired on birth due to genetic alterations. By developing a model carrying pro-arthritogenic factors, MHCII H-2q and Ncf-1 mutation, as well as the pro-atherosclerotic factors, Ldlr-/- and hApoBtg, we have established a new model where both arthritis and atherosclerosis are present. These mice will be used to further characterize the impact of systemic inflammation in the form of arthritis in the atherosclerotic process and vice versa.
    Type of Medium: Online Resource
    ISSN: 1079-5642 , 1524-4636
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 1494427-3
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
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