Professor Stephan Baldus

Organisation / Institute
Department III of Internal Medicine
Cologne University Heart Center

Address

Prof. Stephan Baldus
Department III of Internal Medicine,
Cologne University Heart Center
Kerpener Str. 62
50937 Köln, Germany

stephan.baldus[at]uk-koeln.de

 

 

 Dr. Anna Klinke

Organisation / Institute
Department III of Internal Medicine
Cologne University Heart Center

Address

Dr. Anna Klinke
Department III of Internal Medicine,
Cologne University Heart Center
Kerpener Str. 62
50937 Köln, Germany

anna.klinke[at]uk-koeln.de

Project summary:

Myeloperoxidase-mediated modulation of glycocalyx integrity and its impact on vascular dysfunction

Vascular inflammatory processes are critically linked with the pathogenesis of various cardiovascular diseases. Impairment of vascular integrity implies disturbance of the endothelial glycocalyx, which represents a gel-like structure lining the blood vessels. It is mainly comprised of protein-bound glucosaminoglycans and serves as a critical regulator of vascular function influencing endothelial permeability, blood flow velocity, shear-mediated production of nitric oxide and leukocyte extravasation. Due to electrostatic interactions the highly cationic heme enzyme myeloperoxidase (MPO), which is abundantly expressed and released by polymorphonuclear neutrophils (PMN), avidly binds to the endothelial glycocalyx. MPO exerts potent pro-oxidant and pro-inflammatory properties and has been identified as a mediator of endothelial dysfunction and atherosclerosis. It has been shown recently, that MPO binding to the glycocalyx decreases the electrostatic repulsion between the endothelium and the leukocyte’s surface thereby inducing leukocyte recruitment, which represents a critical inflammatory event.

The current project aims to further characterize MPO’s impact on the endothelial glycocalyx and the consequences of the interaction on vascular integrity. Cell culture and in-vivo techniques using wild-type and MPO-deficient mice will be employed. Glycocalyx charge and structure upon MPO exposure will be determined by histological and immunofluorescence staining and by electron microscopy. Endothelial permeability, microhemorheology and mechanotransduction will be investigated in cultured cells under flow conditions and in mice using intravital microscopy of postcapillary venules of the cremaster muscle.

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A) Immunofluorescence staining of MPO (green) in a WT mouse cremasteric venule upon intraarterial saline or MPO-infusion.  Alcian blue dye staining, a marker of negatively charged glycosaminoglycans,  is less pronounced upon MPO-infusion. Bar = 25 µm. 
B) Adherent leukocytes in a cremasteric venule upon MPO infusion visualized by intravital microscopy. Bar = 10µm.

General research interest

  • Role of leukocyte-dependent inflammatory processes for cardiac and vascular plasticity: Molecular mechanisms of leukocyte-mediated 1) endothelial and myocardial dysfunction and 2) vascular and myocardial maladaptive structural remodeling  
  • Significance of leukocytes for pathogenesis of heart failure, cardiac reperfusion injury, cardiac arrhythmias and pulmonary hypertension  
  • Leukocyte-derived peroxidases as novel therapeutic targets in cardiovascular disease    

 

Prof. Stephan Baldus  

Prof. Stephan Baldus attended the Medical School at the University of Ulm and Hamburg and graduated 1996 in Hamburg. His residency in the Department of Cardiology at the University of Hamburg from 1996 – 1998 and at the Kerckhoff Clinic in Bad Nauheim in 1999 was followed by a position as a postdoctoral research fellow in the laboratory of Prof. Bruce Freeman at the Centre for Free Radical Biology at the University of Alabama at Birmingham, USA from 1999 – 2001. Thereafter, he continued his medical training at the University Heart Centre Hamburg and became an independent group leader supervising clinical and experimental research. In 2004 he received the board approval for Internal Medicine and in 2006 he became an assistant professor at the University Heart Centre Hamburg receiving the board approvals for Cardiology and Intensive Care Medicine in 2007 and 2012. In 2010 he obtained a position as associate professor and vice chair at the department of cardiology at the University Heart Centre Hamburg, which he hold until 2012. Today, he is Full Professor at the University of Cologne and Director of the Department of Internal Medicine and Cardiology at the Heart Centre, University of Cologne. In addition, he is Chair of the Cologne Cardiovascular Research Centre and senior supervisor of the Cluster of Inflammation and Redox Signaling at the University Heart Centre. His work has been acknowledged amongst others by the Albert Fraenkel Award of the German Society of Cardiology in 2008 and the Paul Schölmerich Award of the German Society of Internal Medicine in 2010.    

 

Dr. Anna Klinke  

Dr. Anna Klinke finished her studies of Pharmacy at the University of Münster in 2005. She became PhD student in the laboratory of Prof. Baldus at the University Heart Centre Hamburg and passed collaboration and training attendances in the Czech Academy of Science in Brno, Czech Republic and the Walter Brendel Centre of Experimental Medicine of the LMU Munich. After obtaining her doctoral degree in 2009, she became junior Principal Investigator in the Institute of Experimental Cardiology at the University Heart Centre Hamburg and the Cardiovascular Research Centre Hamburg in 2010. In 2012 she moved with Prof. Baldus to Cologne and established the experimental laboratory at the University of Cologne. Today, she is laboratory supervisor leading one of the groups of the Cluster of Inflammation and Redox Signaling at the Heart Centre in Cologne embedded in the Cardiovascular Research Centre.