- Andreas Bergthaler Group
- Christoph Binder Group
- Christoph Bock Group
- Sylvia Knapp Group
- Robert Kralovics Group
- Stefan Kubicek Group
- Joanna I. Loizou Group
- Jörg Menche Group
- Giulio Superti-Furga Group
- Georg Winter Group
- Chemical Screening, Proteomics and Metabolomics Facility
- Biomedical Sequencing Facility (BSF)
- Keiryn Bennett (Senior Researcher on Leave)
CeMM Principal Investigator
Department of Medical and Chemical Laboratory Diagnostics, Medical University of Vienna
Immunity and Atherosclerosis
Oxidation-specific epitopes in atherosclerosis
During the development of atherosclerotic lesions, low-density lipoproteins (LDL) deposit in the wall of large and medium-sized arteries, where they become oxidized and are taken up by infiltrating macrophages resulting in the formation of foam cells. This process is also characterized by inflammatory reactions and the accumulation of oxidized LDL as well as apoptotic cells in the vascular wall. Notably, both oxidized LDL and apoptotic cells carry the same oxidation-specific epitopes (OSE), which represent danger-associated molecular patterns that are recognized by the innate immune system.
We hypothesize that OSE are key drivers of the inflammatory response in atherosclerosis. Therefore we are investigating how macrophages sense OSE and study the functional consequences of this in the development of atherosclerotic lesions. Key areas include the identification of the receptors and molecular pathways that are mediating these effects, and the development of strategies to inhibit these specific inflammatory responses.
Natural antibodies and the complement system in atherosclerosis
Natural antibodies are pre-existing germline-encoded antibodies that are primarily of the IgM class and secreted by a specialized subset of B1 cells. They play an important role in the first line defense against microbial infections and provide important “house keeping” functions by recognizing damaged self antigens. Natural IgM protect mice from atherosclerotic lesion formation, and data from our group demonstrated that a large part of natural IgM antibodies has specificity for OSE. Ongoing projects focus on the identification of the mechanism by which natural IgM mediate atheroprotection and whether the recognition of OSE is a critical part of this. Moreover, we are pursuing strategies that focus on the therapeutic induction of natural IgM.
More recently we discovered that complement factor H (CFH) specifically binds and neutralizes one type of OSE, namely malondialdehyde modifications. CFH is a major inhibitor of complement activation and genetic variants of it have been associated with a number of disease conditions. We are currently investigating if and how this newly found property of CFH plays a role in atherosclerosis and other inflammatory diseases.
Christoph Binder obtained his MD degree at the University of Vienna in 1997 and received his Ph.D. in Molecular Pathology at the University of California San Diego (UCSD) in 2002. Following a postdoctoral training period at UCSD, he joined the Department of Laboratory Medicine of the Medical University of Vienna and became Principal Investigator at CeMM in 2006. In 2009 he was appointed Professor of Atherosclerosis Research at the Medical University of Vienna. Christoph Binder is dually affiliated with CeMM and the Medical University of Vienna.
Cardilo-Reis L, et al. Interleukin-13 protects from atherosclerosis and modulates plaque composition by skewing the macrophage phenotype. EMBO Mol Med. 2012 Oct;4(10):1072-86. (abstract)
Weismann D, et al. Complement factor H binds malondialdehyde epitopes and protects from oxidative stress. Nature.2011 Oct 5;478(7367):76-81. (abstract)
Chou MY, et al. Oxidation-specific epitopes are dominant targets of innate natural antibodies in mice and humans.J Clin Invest.2009 May;119(5):1335-49. (abstract)
Binder CJ, et al. Pneumococcal vaccination decreases atherosclerotic lesion formation: molecular mimicry between Streptococcus pneumoniae and oxidized LDL.Nat Med.2003 Jun;9(6):736-43. (abstract)
Binder CJ, et al. Innate and acquired immunity in atherogenesis. Nat Med. 2002 Nov;8(11):1218-26. (abstract)