About the lab

The group studies interconnections of the immune system and cardiovascular diseases. A special focus lies on the interactions of immune cells with the vessel wall as well as with each other in the context of vascular disease and atherosclerosis. Platelets are considered as immune cells in this context and we place an emphasis on the discovery of platelet-immune cell interactions and non-hemostatic functions of platelets or the impact of the complement system on platelet biology. Connecting these research questions, we are interested in mechanisms of vessel growth in the adult organism, i.e. regeneration after ischemic events and restoration of perfusion after vessel occlusion.

Featured research (16)

Cardiovascular diseases (CVD) constitute the main cause of death worldwide. Both inflammation and oxidative stress have been reported to be involved in the progress of CVD. It is well known that generation of oxidative stress during the course of CVD is involved in tissue damage and inflammation, causing deleterious effects such as hypertension, dysfunctional metabolism, endothelial dysfunction, stroke, and myocardial infarction. Remarkably, natural antioxidant strategies have been increasingly discovered and are subject to current scientific investigations. Here, we addressed the activation of immune cells in the context of ROS production, as well as how their interaction with other cellular players and further (immune) mediators contribute to metabolic and cardiovascular disorders. We also highlight how a dysregulated complement system contributes to immune imbalance and tissue damage in the context of increases oxidative stress. Additionally, modulation of hypothalamic oxidative stress is discussed, which may offer novel treatment strategies for type-2 diabetes and obesity. Together, we provide new perspectives on therapy strategies for CVD caused by oxidative stress, with a focus on oxidative stress.
Platelets contribute to the regulation of tissue neovascularization, although the specific factors underlying this function are unknown. Here, we identified the complement anaphy-latoxin C5a-mediated activation of C5a receptor 1 (C5aR1) on platelets as a negative regulatory mechanism of vessel formation. We showed that platelets expressing C5aR1 exert an inhibitory effect on endothelial cell functions such as migration and 2D and 3D tube formation. Growth factor-and hypoxia-driven vascularization was markedly increased in C5ar1 −/− mice. Platelet-specific deletion of C5aR1 resulted in a proangiogenic phenotype with increased collateralization, capillarization and improved pericyte coverage. Mechanistically, we found that C5a induced preferential release of CXC chemokine ligand 4 (CXCL4, PF4) from platelets as an important antiangiogenic paracrine effector molecule. Interfering with the C5aR1-CXCL4 axis reversed the antiangiogenic effect of platelets both in vitro and in vivo. In conclusion, we identified a mechanism for the control of tissue neovascularization through C5a/C5aR1 axis activation in platelets and subsequent induction of the antiangiogenic factor CXCL4.
Platelets contribute to the regulation of tissue neovascularization, although the specific factors underlying this function are unknown. Here, we identified the complement anaphylatoxin C5a-mediated activation of C5a receptor 1 (C5aR1) on platelets as a negative regulatory mechanism of vessel formation. We showed that platelets expressing C5aR1 exert an inhibitory effect on endothelial cell functions such as migration and 2D and 3D tube formation. Growth factor- and hypoxia-driven vascularization was markedly increased in C5ar1 −/− mice. Platelet-specific deletion of C5aR1 resulted in a proangiogenic phenotype with increased collateralization, capillarization and improved pericyte coverage. Mechanistically, we found that C5a induced preferential release of CXC chemokine ligand 4 (CXCL4, PF4) from platelets as an important antiangiogenic paracrine effector molecule. Interfering with the C5aR1-CXCL4 axis reversed the antiangiogenic effect of platelets both in vitro and in vivo. In conclusion, we identified a mechanism for the control of tissue neovascularization through C5a/C5aR1 axis activation in platelets and subsequent induction of the antiangiogenic factor CXCL4.
A mutual relationship exists between immune activation and mechanisms of thrombus formation. In particular, elements of the innate immune response such as the complement system can modulate platelet activation and subsequently thrombus formation. Several components of the complement system including C3 or the membrane attack complex have been reported to be associated with platelets and become functionally active in the micromilieu of platelet activation. The exact mechanisms how this interplay is regulated and its consequences for tissue inflammation, damage or recovery remain to be defined. This review addresses the current state of knowledge on this topic and puts it into context with diseases featuring both thrombosis and complement activation.

Lab head

Henry Nording
Department
  • Medizinische Klinik II - Kardiologie, Angiologie, Intensivmedizin (Lübeck)
About Henry Nording
  • Henry Nording currently works at the Department of Internal Medicine, University of Luebeck and is a member of the Cardioimmunology lab at the University of Luebeck. Henry does research in experimental Cardiology.

Members (2)

Lasse Baron
  • Universitätsklinikum Schleswig - Holstein
Jacob von Esebeck
  • Universitätsklinikum Schleswig - Holstein
Anke Constantz
Anke Constantz
  • Not confirmed yet
Elias Rawisch
Elias Rawisch
  • Not confirmed yet
Pauline Raddatz
Pauline Raddatz
  • Not confirmed yet
Natalie Jung
Natalie Jung
  • Not confirmed yet

Alumni (1)

Alexander Hach
Alexander Hach