Christoph Leder

Publications (3)23.93 Total impact

• Article: The bispecific SDF1-GPVI fusion protein preserves myocardial function after transient ischemia in mice.

  Melanie Ziegler, Margitta Elvers, Yvonne Baumer, Christoph Leder, Carmen Ochmann, Tanja Schönberger, Tobias Jürgens, Tobias Geisler, Burkhard Schlosshauer, Oleg Lunov, Stefan Engelhardt, Thomas Simmet, Meinrad Gawaz
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  ABSTRACT: CXCR4-positive bone marrow cells (BMCs) are critically involved in cardiac repair mechanisms contributing to preserved cardiac function. Stromal cell-derived factor-1 (SDF-1) is the most prominent BMC homing factor known to augment BMC engraftment, which is a limiting step of stem cell-based therapy. After myocardial infarction, SDF-1 expression is rapidly upregulated and promotes myocardial repair. We have established a bifunctional protein consisting of an SDF-1 domain and a glycoprotein VI (GPVI) domain with high binding affinity to the SDF-1 receptor CXCR4 and extracellular matrix proteins that become exposed after tissue injury. SDF1-GPVI triggers chemotaxis of CXCR4-positive cells, preserves cell survival, enhances endothelial differentiation of BMCs in vitro, and reveals proangiogenic effects in ovo. In a mouse model of myocardial infarction, administration of the bifunctional protein leads to enhanced recruitment of BMCs, increases capillary density, reduces infarct size, and preserves cardiac function. These results indicate that administration of SDF1-GPVI may be a promising strategy to treat myocardial infarction to promote myocardial repair and to preserve cardiac function.
  Circulation 02/2012; 125(5):685-96. · 14.74 Impact Factor
• Article: Inhibition of foam cell formation using a soluble CD68-Fc fusion protein.

  Karin Daub, Dorothea Siegel-Axel, Tanja Schönberger, Christoph Leder, Peter Seizer, Karin Müller, Martin Schaller, Sandra Penz, Dagmar Menzel, Berthold Büchele, Andreas Bültmann, Götz Münch, Stephan Lindemann, Thomas Simmet, Meinrad Gawaz
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  ABSTRACT: The appearance of lipid-rich foam cells is a major feature of vulnerable atherosclerotic plaque formation. The transformation of macrophages into foam cells results from excessive uptake of cholesterol-rich particles by scavenger receptors such as CD68. We cloned a CD68-Fc immunoadhesin, a fusion protein consisting of the extracellular domain of the human CD68 and a human Fc domain, and investigated the function in vitro. Specific binding of CD68-Fc to OxLDL with an affinity of 10 nmol/L was determined by surface plasmon resonance and increased binding to lipid-rich human and ApoE(-/-) mice plaque tissue. This was confirmed both by immunohistochemical staining of CD68-Fc-treated paraffin sections from human plaques and by ELISA-based quantification of CD68-Fc binding to human atherosclerotic plaque extracts. In an in vitro model of macrophage/foam cell formation, CD68-Fc reduced foam cell formation significantly. This was caused both by interference of CD68-Fc with OxLDL uptake into macrophages and platelets and by the inhibition of platelet/OxLDL phagocytosis. Finally, expression of metalloproteinases by macrophages/foam cells was inhibited by CD68-Fc. In conclusion, CD68-Fc seems to be a promising new tool for preventing macrophage/foam cell formation. Thus, CD68-Fc might offer a novel therapeutic strategy for patients with acute coronary syndrome by modulating the generation of vulnerable plaques.
  Journal of Molecular Medicine 05/2010; 88(9):909-20. · 4.67 Impact Factor
• Article: Modulating immune responses and inflammation.

  Christoph Leder, Melanie Ziegler, Meinrad Gawaz
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  ABSTRACT: New disease-modifying therapeutic options for immune diseases in general and immune-related cardiovascular diseases are urgently needed. Various innovative therapies are currently developed ranging from small molecules and natural compounds to biopharmaceuticals. This article summarizes the overview of possible points of intervention for an ongoing immune response and lists examples of currently developed therapeutic exploitations of these targets. Research and development for the treatment of autoimmune and inflammatory diseases in general will most likely be fruitful also for therapy of immune-related cardiovascular diseases such as myocarditis and atherosclerosis and should be closely followed by research groups focused on cardiovascular immunology.
  Seminars in Thrombosis and Hemostasis 03/2010; 36(2):219-22. · 4.52 Impact Factor