Select languageSelect language
Institute of Physiology and Pathophysiology

Wagner Group

This page requires JavaScript for full functionality.

Group Members

Endothelial Cell-Platelet-Leukocyte Interaction in Vascular Remodelling: Role of CD40/CD154-Mediated Co-Stimulation

(Project C6/Hecker, SFB / Transregio 23 "Vascular Differentiation and Remodeling" Dies ist ein externer Link)

 

Pegah Khamehgir-Silz, Su-Hwan Kim (Research Training Group), Sebastian Lont, Cheryl Sultan, Andreas H. Wagner

 

CD40 is a cell surface receptor belonging to the tumour necrosis factor receptor family. It is constitutively expressed by antigen-presenting cells such as monocyte/macrophages but also by non-immune cells like endothelial cells. The CD40 ligand (CD154), originally identified as a surface marker of activated T cells, is also present on activated platelets which release numerous bioactive mediators capable of modulating innate immune cells, activating endothelial cells, and influencing systemic immune responses. In endothelial cells, CD40-CD154 interaction causes a marked increase in the expression of pro-inflammatory adhesion molecules and chemokines which, in turn, promote the homing and extravasation of T cells, namely type 1 T-helper (Th1) cells, and monocyte/macrophages. In the vessel wall, Th1 cell differentiation and activity may additionally be controlled by natural T-regulatory cells (Treg) which are frequently detected in early atherosclerotic lesions. Moreover, the transmigration of both types of lymphocytes as well as that of monocytes through the endothelial cell monolayer might be facilitated by platelets present at the endothelial cell junctions.

 

The aim of this project is to examine the relative extent by which CD40-CD154 driven endothelial cell-leukocyte, endothelial cell-platelet and/or platelet-leukocyte interactions contribute to the initiation and/or maintenance of atherosclerosis. It  focuses on the interaction of Th1 cells, Treg and monocytes with both endothelial cells and platelets as well as with each other, and primarily employs reverse genetics techniques in vitro (human cultured cells) and in vivo (mouse).


CD154 induced changes in gene expression in endothelial cells and their consequences for endothelial cell-leukocyte interaction.

Protein Oxidation in Vascular Cells as Protective Mechanism against Diabetic Angiopathy

(Projekt International Research Training Group 1874/1 "Diabetic Microvascular Complications") Dies ist ein externer Link)

 

Christoph Hangel, Tanja Wiedenmann, Andreas H. Wagner, Markus Hecker

 

It is virtually certain that reactive oxygen (ROS) and nitrogen (RNS) species contribute to diabetic vascular lesions. Hyperglycaemia, for example, leads to the protein carbonylation and nitration by increased oxidative and nitrosative stress, respectively. Glucose-derived dicarbonyl oxidation products such as methylglyoxal (MG) increase mitochondrial formation of superoxide anions (O2) which can react with nitrogen monoxide (NO) to form peroxynitrite (nitration) in endothelial cells, and, via hydrogen peroxide (H2O2) and the Fe2+-dependent Fenton reaction, hydroxyl radicals (carbonylation), respectively.


This project aims at analysing the role of oxidative protein modifications as a potential protective mechanism of vascular cells against late diabetic lesions, and diabetic macroangiopathy in particular.

Inhibition of Aortic Elastolysis by Decoy Oligodeoxynucleotides-Mediated Inhibition of Transcription of Matrix Metalloproteinases in the Fibrillin-1 Deficient Mouse mgR/mgR (Marfan model)

(supported by the B. Braun-Stiftung, Melsungen Dies ist ein externer Link)

 

Anca Remes, Andreas H. Wagner
Clinic for Cardiac Surgery, Heidelberg University Hospital: Rawa Arif, Klaus Kallenbach

 

Quite often vascular changes associated with the Marfan syndrome, such as aortic aneurysms or aortic dissections, threaten the lifes of those afflicted already in childhood. To date no causal therapy of this genetic disease of the connective tissue exists. The vascular component of the Marfan syndrome is pathophysiologically characterised by an abnormally high activity of matrix metalloproteinases (MMPs) in smooth muscle cells of the aortic wall. This group of enzymes causes elastolysis in the aortic media thereby contributing to the progressing destablisation of the vascular wall.

The homozygose fibrillin-1 deficient mouse (mgR/mgR) is an accepted small animal model for the Marfan syndrome. Similar to patients with the Marfan syndrome, it shows an elevated MMP activity in the smooth muscle cells of the aortic wall in combination with an age-dependent increased fragmentation of elastic fibres. Employing the Marfan mouse model, we want to inhibit the expression of MMP, and as a consequence reduce their activity, by incubating aortic fragments with decoy oligodeoxynucleotides (dODN) ex vivo

Gene Therapy of Transplantation Vasculopathy

(supported by the Dietmar Hopp Stiftung gGmbH, St. Leon-RotDies ist ein externer Link)

 

Andreas H. Wagner
Clinic for Cardiac Surgery, Heidelberg University Hospital: Rawa Arif, Klaus Kallenbach
Initernal Medicine III, Division of Cardiology, Angiology and Pneumology, Heidelberg University Hospital: Oliver Müller

 

Project description on the website of the Dietmar Hopp Foundation (in German).


Recent Publications

*

Selective vulnerability of αOFF retinal ganglion cells during onset of autoimmune optic neuritis. Neuroscience. 2018 Nov 21;393:258-272. doi: 10.1016/j.neuroscience.2018.07.040. Epub 2018 Aug 1.

*

Genetic ablation of NFAT5/TonEBP in smooth muscle cells impairs flow- and pressure-induced arterial remodeling in mice. FASEB J. 2018 Nov 1:fj201801594R. doi: 10.1096/fj.201801594R. [Epub ahead of print]

*

Synaptic entrainment of ectopic action potential generation in hippocampal pyramidal neurons.  J Physiol. 2018 Nov;596(21):5237-5249. doi: 10.1113/JP276720. Epub 2018 Sep 19.

*

The Long Noncoding RNA Cancer Susceptibility 9 and RNA Binding Protein Heterogeneous Nuclear Ribonucleoprotein L Form a Complex and Coregulate Genes Linked to AKT Signaling. Hepatology. 2018 Nov;68(5):1817-1832. doi: 10.1002/hep.30102. Epub 2018 Oct 12.

*

Reduction of Transplant Vasculopathy by Intraoperative Nucleic Acid-based Therapy in a Mouse Aortic Allograft Model. Thorac Cardiovasc Surg. 2018 Oct 23. doi: 10.1055/s-0038-1673633. [Epub ahead of print]

*

Early appearance and spread of fast ripples in the hippocampus in a model of cortical traumatic brain injury. J Neurosci. 2018 Oct 17;38(42):9034-9046. doi: 10.1523/JNEUROSCI.3507-17.2018. Epub 2018 Sep 6.

*

High-fat diet suppresses the positive effect of creatine supplementation on skeletal muscle function by reducing protein expression of IGF-PI3K-AKT-mTOR pathway. PLoS One. 2018 Oct 4;13(10):e0199728. doi: 10.1371/journal.pone.0199728. eCollection 2018.

*

Alcohol reduces muscle fatigue through atomistic interactions with nicotinic receptors. Commun Biol. 2018 Oct 3;1:159. doi: 10.1038/s42003-018-0157-9. eCollection 2018.

*

Possible neurotoxicity of the anesthetic propofol: evidence for the inhibition of complex II of the respiratory chain in area CA3 of rat hippocampal slices. Arch Toxicol. 2018 Oct;92(10):3191-3205. doi: 10.1007/s00204-018-2295-8. Epub 2018 Aug 24.

*

Endothelial progenitor cells accelerate endothelial regeneration in an in vitro model of Shigatoxin-2a-induced injury via soluble growth factors. Am J Physiol Renal Physiol. 2018 Oct 1;315(4):F861-F869. doi: 10.1152/ajprenal.00633.2017. Epub 2018 Mar 7.

*

Strategy for marker-based differentiation of pro- and anti-inflammatory macrophages using matrix-assisted laser desorption/ionization mass spectrometry imaging. Analyst. 2018 Sep 10;143(18):4273-4282. doi: 10.1039/c8an00659h. Epub 2018 Jul 20.

*

Recent advances in hippocampal structure and function. Cell Tissue Res. 2018 Sep;373(3):521-523. doi: 10.1007/s00441-018-2913-z. Epub 2018 Aug 20. doi: 10.1007/s00441-018-2913-z. Editorial. No abstract available.

*

Electrical coupling between hippocampal neurons: contrasting roles of principal cell gap junctions and interneuron gap junctions. Cell Tissue Res. 2018 Sep;373(3):671-691. doi: 10.1007/s00441-018-2881-3. Epub 2018 Aug 15. Review.

*

Metabolic modulation of neuronal gamma-band oscillations. Pflugers Arch2018 Sep;470(9):1377-1389. doi: 10.1007/s00424-018-2156-6. Epub 2018 May 28.

*

The VAMP-associated protein VAPB is required for cardiac and neuronal pacemaker channel function. FASEB J. 2018 Jun 7:fj201800246R. doi: 10.1096/fj.201800246R. [Epub ahead of print]


Institute of
Physiology and Pathophysiology

Heidelberg University

Im Neuenheimer Feld 326

69120 Heidelberg

Germany

Phone:+49 6221 54-4035
Fax:+49 6221 54-4038
E-mail:sekretariat.hecker@
physiologie.uni-heidelberg.de