Toll-like receptors and cytokines.
        TheScientificWorldJOURNAL (2011)11_981
Grote K, Schütt H, Schieffer B. Toll-Like Receptors in Angiogenesis. TheScientificWorldJOURNAL.2011;11:981-91

  Innovative Therapeutic Approaches for the Prevention of Atherosclerotic Plaque Development

A major focus is the pathogenesis of atherosclerotic plaque development and the associated pathological remodeling in the vessel wall. Of special interest is the role of cells and components of innate and adaptive immunity and their interaction with endothelial cells. In this context, vascular inflammation and its mediators (cells, cytokines and chemokines) and their role in the formation of atherosclerotic plaques are studied in animal models and patients with coronary heart disease. The aim is to identify innovative therapeutic interventions for interfering with plaque development, plaque instability and vascular maladaptation as outlined: Schuett H, Schieffer B.Targeting cytokine signaling as an innovative therapeutic approach for the prevention of atherosclerotic plaque development. Curr Atheroscler Rep. 2012;14:187-9.

Projects currently studied in the group of Dr. Jutta Schütt and Prof. Dr. Bernhard Schieffer were supported by SFB 566 (gpl30-abhängige Akute Phase Reaktion: Innovative Therapieansätze zur Prävention atherosklerotischer Gefäßerkrankungen)

Our current projects
Animal models
(ApoE-/ -, LDL-R-/ -) have been established where hypercholesterolemia is a major cause of atherosclerosis. In special mouse models, we study SOCS proteins as negative regulators of inflammatory processes and the immunologically important chemokine receptor CCR7 and Toll-like receptors (TLRs) as important receptors of innate immunity. In addition, we develop a humanized mouse model in which the cells of the innate and acquired immunity are of human origin. Extensive patient studies coupled with genetic risk assessment will become of great importance for our applied clinical research.

Selected publications

Luchtefeld M, Grothusen C, Gagalick A, Jagavelu K, Schuett H, Tietge UJ, Pabst O, Grote K, Drexler H, Förster R, Schieffer B. Chemokine receptor 7 knockout attenuates atherosclerotic plaque development. Circulation. 2010;122:1621-8.

Schieffer B, Luchtefeld M. Importance of CCR7 for migration of immune cells in atherosclerosis and vascular remodeling. Emerging role of chemokine receptor 7 in atherosclerosis. Trends Cardiovasc Med. 2011;21:211-6.

Jagielska J, Kapopara PR, Salguero G, Scherr M, Schütt H, Grote K, Schieffer B, Bavendiek U. Interleukin-1 assembles a proangiogenic signaling module consisting of caveolin-1, tumor necrosis factor receptor-associated factor 6, p38-mitogen-activated protein kinase (MAPK), and MAPK-activated protein kinase 2 in endothelial cells. Arterioscler Thromb Vasc Biol. 2012;32:1280-8.

Schuett H, Oestreich R, Waetzig GH, Annema W, Luchtefeld M, Hillmer A, Bavendiek U, von Felden J, Divchev D, Kempf T, Wollert KC, Seegert D, Rose-John S, Tietge UJ, Schieffer B, Grote K. Transsignaling of interleukin-6 crucially contributes to atherosclerosis in mice. Arterioscler Thromb Vasc Biol. 2012;32:281-90.

Grothusen C, Schuett H, Hillmer A, Lumpe S, Grote K, Ballmaier M, Bleich A, Glage S, Tietge UJ, Luchtefeld M, Schieffer B. Role of suppressor of cytokine signaling-1 in murine atherosclerosis.PLoS One. 2012;7:e51608. doi: 10.1371/journal.pone.0051608.

Grote K, Sonnenschein K, Kapopara PR, Hillmer A, Grothusen C, Salguero G, Kotlarz D, Schuett H, Bavendiek U, Schieffer B.  Toll-Like Receptor 2/6 Agonist Macrophage-Activating Lipopeptide-2 Promotes Reendothelialization and Inhibits Neointima Formation After Vascular Injury.
Arterioscler Thromb Vasc Biol. 2013;33:2097-2104.

Lukasz A, Beutel G, Kümpers P, Denecke A, Westhoff-Bleck M, Schieffer B, Bauersachs J, Kielstein JT, Tutarel O. Angiopoietin-2 in adults with congenital heart disease and heart failure. PLoS One. 2013 Jun 24;8(6):e66861. doi: 10.1371/journal.pone.0066861. Print 2013.
Rupp TP, Rupp KG, Alter P, Rupp H. Replacement of Reduced Highly Unsaturated Fatty Acids (HUFA Deficiency) in
Dilative Heart Failure: Dosage of EPA/DHA and Variability of Adverse Peroxides
and Aldehydes in Dietary Supplement Fish Oils. Cardiology. 2013;125:223-31.

  • Development of a humanized mouse model for studies on the interaction of human cells of adaptive immunity in atherosclerosis and the use of specific human therapies.
  • In vitro modulation of the immune repertoire by atherogenic substances and identification of atherosclerosis-specific clonal expansion of certain T cell receptors by spectratyping.
  • Role of suppressor of cytokine signaling (SOCS) -1 in early atherogenesis and its influence on the activation of pro-inflammatory monocytes.
  • Studies on the interaction of dendritic cells and naive T cells in an atherosclerotic mouse model.
  • Investigations on the role of NOD-like receptors in atherosclerosis and vascular remodeling.
  • Visualization of the development and progression of atherosclerotic plaques as well as the migration and interaction of immune cells in atherogenesis using 7 T MRI.
  • Importance of CCR7 for migration of immune cells in atherosclerosis and vascular remodeling.
  • In view of the JELIS trial and the pioneering studies of Calder et al. on plaque stabilization by EPA, it will be examined whether deficiency of highly unsaturated fatty acids (HUFA) involving also EPA+DHA during progression of dilative heart failure is associated with destabilization of plaques and an increased risk of infarction.
  • Using stable isotope (C13) precursor labeling, it will be assessed (mass spectrometry) in macrophage-like cell lines RAW 246.7 and J774.1 to what extent the synthesis of omega-3 over omega-6 HUFA can be increased. Increased omega-3 HUFA are expected to alter the phenotype of macrophages possibly towards the anti-inflammatory phenotype, thereby contributing to plaque stabilization.

        Schieffer/Dr. Schütt

Dr. Jutta Schütt
Laboratory director

Tel: 06421-2821929

E-mail: Jutta.Schuett(at)

Prof. Dr. Bernhard Schieffer
Director, Department of Cardiology and Angiology
Baldingerstrasse, D-35043 Marburg
Tel. 06421-5866462, Fax 06421-5868954

22.12.2013 (HR)