Startseite » Research » Project Funding » DFG FOR809

DFG Forschergruppe 809

DFGblau134zu74

Chemokines and adhesion molecules in cardiovascular pathogenesis

 

Atherosclerosis is characterized by chronic inflammation of the arterial wall, initiated by endothelial dysfunction and structural alterations followed by lesion progression in the major arteries. The underlying pathology is characterized by monocytes- and T cells infiltration into the developing vascular lesion (Weber & Noels, Nat Med 2011). The consequential disorders like vascular occlusion and thrombosis often result in myocardial infarction and ischemic stroke which are rapidly becoming the leading cause of death and morbidity worldwide with over 7 Mio casualties annually in the Western world.

Several studies have recently highlighted the importance of chemokines and chemokine-like cytokines like MIF and their receptors (e.g. CXCR2, CCR5) during atherosclerosis progression. Nevertheless, little is known about the pathophysiological mechanisms underlying the vascular inflammation in the context of atherosclerosis. Furthermore, similar to the leucocytes recruitment during inflammation, adhesion molecules (e.g. P-selectin, VCAM-1), integrin ligands like junctional adhesion molecules (e.g. JAM-A) and potential antagonists (e.g. Del-1) may play crucial role in the atherosclerosis progression. Moreover, chemokines interact during different steps of progressive recruitment (e.g. cell arrest vs. diapedesis) or during lesion development (early lesion vs. advanced plaque). There is a tendency, at least to a certain extent, pointing out a specificity of certain mononuclear cell population (e.g. in the case of CCL17, CXCR6) or of monocytes subpopulations. Furthermore, the interaction between different proatherogenic and protective mononuclear cell populations in systemic and local immune response in plaque (e.g. anti-inflammatory regulatory T cells and unexpected proatherogenic characteristics of neutrophils) are in particular focus. The aim of the program project research group FOR809 is to investigate the pathophysiological contribution of the individual mononuclear subpopulations, their released products and chemokines in the context of vascular recruitment and plaque development. The program project research group FOR809 includes 12 different subprojects (P).

P1 investigates the structural and functional characteristics of MIF/chemokine receptors axis (CXCR2/4/7 interactions) in animal model of atherosclerosis and myocardial infarction. In addition to receptor complexes study, structure-function analysis and therapeutic targeting of the chemokine interactome, especially chemokine heteromer formation in platelets have to be explored (P2). Furthermore, the aim of P3 is to study the functional role of dendritic cells and associated chemokines in immune- and vascular response during atherosclerosis development. Moreover, studying the role of chemokine CXCL12 and its receptors CXCR4 and CXCR7 in vascular homeostasis and vascular remodeling (P4), as well as microRNA-mediated functional CXCL12 induction (P4) and LPA- and HIF-1α-mediated signal transduction (P8) will improve our knowledge regarding the pathophysiology of atherosclerosis development. P6 focuses on junctional adhesion molecule JAM-A, the discovering of other integrin ligands and receptor interactions in inflammatory cell recruitment and atherogenesis. Further studies include investigations of new chemokine-like alarmins and their role as effectors of neutrophil granulocytes (P9), as well as new studies about differential function of monocytes subpopulations in cardiometabolic disorders (P10) and function of co-stimulatory pathways in atherosclerosis progression (P11). Finally, P12 explores non-invasive imaging of atherosclerosis-associated marker molecules (e.g. JAM-A, MKEY) and cell functions using ultrasound- and multiphoton-based techniques and provides a multimodal platform for molecular atherosclerosis imaging using fluorescence tomography, multiphoton microscopy and µ-computed tomography.

 

Spokesman: Prof. Dr. Med C. Weber

 

Subprojects:

FOR809_scheme overview_scaled

 

 


TP2: Analyse der Struktur-Funktions-Beziehung der Wechselwirkung thrombozytäre Chemokine in der Atherogenese

Philipp v. Hundelshausen (Förderung HU 1618/1-2)


TP3: Vaskuläre dendritische Zellen in der Atherosklerose

Alma Zernecke (laufende Förderung ZE 827/1−2)


TP4: Rolle der CXCL12 Rezeptoren CXCR4 und CXCR7 in der Atherosklerose

und vaskulären Zellhomöostase

Christian Weber (laufende Förderung WE 1913/11-2)


TP6: Charakterisierung alternativer LFA-1 Liganden bei entzündlicher

und atherogener Zellrekrutierung

Rory Koenen (laufende Förderung KO 2948/1-2)


TP8: Regulation der CXCL12 Expression bei der stammzellvermittelten vaskulären

Wundheilung durch Lysophosphatidsäure und hypoxia inducible factor (HIF)-1α

Andreas Schober (laufende Förderung SCHO 1056/3-1)


TP9: Die Rolle von Alarminen aus neutrophilen Granulozyten in der Atherosklerose

Oliver Söhnlein (laufende Förderung SO 876/4-1)


TP10: Differenzielle Funktion von monozytärer Subpopulationen in kardiometabolischen

Erkrankungen

Mihail Hristov (HR 18/1-1)


TP11: Function of co-stimulatory pathways in atherosclerosis

Esther Lutgens (LU 1643/1-1)


TP12: Entwicklung und Erprobung multimodaler molekularer Proben für die

in vivo Charakterisierung der Stabilität atherosklerotischer Plaques

Fabian Kiessling, Marc van Zandvoort, Christian Weber (KI 1072/8-1)


TP Z: Zentralprojekt

Christian Weber (WE 1913/12-2)

 


Auslaufende und assoziierte Teilprojekte

TP5: Die Bedeutung von löslichen und transmembranären Varianten der

Chemokine CX3CL1 und CXCL16 bei vaskulären Entzündungsreaktionen

Andreas Ludwig (laufende Förderung LU869/3-1)


TP7: Chemokine und vaskuläre Adhäsionsmoleküle bei Ischämie/

Reperfusion: Bedeutung von erythrozytärem NO

Marc Merx, Thomas Lauer, Malte Kelm (laufende Förderung ME1821/3-1)



Participating Institutes:

 

 

 

 
 
IPEKlogo

Direktor: Prof. Dr. med. Christian Weber

Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten (IPEK)

 

Pettenkoferstraße 8a & 9

80336 München

 

Tel.: 089-4400-54351

Fax: 089-4400-54352

Mail: Kreislaufinstitut@med.uni-muenchen.de

 

Veranstaltungen

Links