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Grün, NG; Strohmeier, K; Moreno-Viedma, V; Le Bras, M; Landlinger, C; Zeyda, K; Wanko, B; Leitner, L; Staffler, G; Zeyda, M; Stulnig, TM.
Peptide-based vaccination against OPN integrin binding sites does not improve cardio-metabolic disease in mice.
Immunol Lett. 2016; 179(11):85-94 Doi: 10.1016/j.imlet.2016.09.006 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Sommer Nicole
Co-Autor*innen der Med Uni Graz
Leitner Lukas

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Obesity causes insulin resistance via a chronic low-grade inflammation. This inflammation is characterized by elevated pro-inflammatory markers and macrophage accumulation in the adipose tissue (AT). AT inflammation is a key factor causing insulin resistance and thus type 2 diabetes, both linked to atherosclerotic cardiovascular disease. Osteopontin (OPN), a well-known inflammatory cytokine, is involved in obesity-linked complications including AT inflammation, insulin resistance, atherosclerosis and CVD. During inflammation, OPN is proteolytically cleaved by matrix metalloproteinases or thrombin leading to increased OPN activity. Therefore, OPN provides a new interesting target for immunological prevention and treatment of obesity-associated diseases. The aim of our study was to evaluate peptide-based vaccines against integrin binding sites of OPN and to examine whether these active immunotherapies are functional in reducing metabolic tissue inflammation, insulin resistance, and atherosclerosis in a cardio-metabolic (Ldlr-/- mice) and a diet-induced obesity model (WT mice). However, atherosclerosis, insulin resistance and AT inflammation were not diminished after treatment with OPN-derived peptides in murine models. Lack of efficacy was based on a failure to induce antibodies capable to bind epitopes in the context of functional OPN protein. In conclusion, our data point to unexpected challenges in the immunotherapeutic targeting of adhesive motives, such as RGD containing sequences, on endogenous proteins. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Antibodies - blood
Antibodies - immunology
Atherosclerosis - etiology
Atherosclerosis - metabolism
Atherosclerosis - pathology
Binding Sites - immunology
Biomarkers -
Cross Reactions - immunology
Disease Models, Animal -
Heart Diseases - blood
Heart Diseases - etiology
Heart Diseases - metabolism
Heart Diseases - therapy
Immunization -
Inflammation - etiology
Inflammation - metabolism
Insulin Resistance -
Integrins - chemistry
Integrins - metabolism
Male -
Metabolic Diseases - blood
Metabolic Diseases - etiology
Metabolic Diseases - metabolism
Metabolic Diseases - therapy
Mice -
Mice, Knockout -
Obesity - metabolism
Osteopontin - chemistry
Osteopontin - immunology
Osteopontin - metabolism
Peptide Fragments - administration & dosage
Peptide Fragments - immunology
Protein Binding -
Receptors, LDL - deficiency

Find related publications in this database (Keywords)
Cardio-metabolic disease
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