Medizinische Klinik und Poliklinik I » Forschung/Research » Basic and Translational Research » Research Areas » Mechanisms of sterile inflammation in cardiovascular diseases

Mechanisms of sterile inflammation in cardiovascular diseases

LysM 

Sterile inflammation is the pathophysiologic basis of cardiovascular diseases like atherosclerosis, thrombosis and myocardial infarction. We focus on identifying new cellular and molecular factors causing these diseases by connecting the fields of thrombosis and inflammation. In sterile inflammation, we could show that non-immune perivascular cells – namely pericytes – control interstitial leukocyte migration to a focus of necrosis and instruct myeloid leukocytes with pattern recognition and motility programs. In current projects, we are investigating the contribution of perivascular cells to systemic diseases like atherosclerosis (SFB1123).

The second focus is the analysis of the processes leading to venous thrombosis. This common diseases shares many similarities to sterile inflammation and this mechanism is essential to trigger activation of the coagulation system in this setting. Therefore, we are investigating the cellular and molecular factors initiating this inflammatory process in order to develop new targeted therapies which can prevent venous thrombosis without primarily impairing the coagulation system. In addition, we characterize the pathophysiology of venous thrombosis in different settings like stasis and malignant diseases (DFG-ANR project).

  

PI Konstantin Stark  konstantin.stark@med.uni-muenchen.de

 

 

Key publications:

 

Blood 2016

Disulfide HMGB1 derived from platelets coordinates venous thrombosis in mice.

Stark K, Philippi V, Stockhausen S, Busse J, Antonelli A, Miller M, Schubert I, Hoseinpour P, Chandraratne S, von Brühl ML, Gaertner F, Lorenz M, Agresti A, Coletti R, Antoine DJ, Heermann R, Jung K, Reese S, Laitinen I, Schwaiger M, Walch A, Sperandio M, Nawroth PP, Reinhardt C, Jäckel S, Bianchi ME, Massberg S.

Blood. 2016 Nov 17;128(20):2435-2449.


Capillary and arteriolar pericytes attract innate leukocytes exiting through venules and 'instruct' them with pattern-recognition and motility programs.

Stark K, Eckart A, Haidari S, Tirniceriu A, Lorenz M, von Brühl ML, Gärtner F, Khandoga AG, Legate KR, Pless R, Hepper I, Lauber K, Walzog B, Massberg S.

Nat Immunol. 2013 Jan;14(1):41-51. doi: 10.1038/ni.2477. Epub 2012 Nov 25.

 

Monocytes, neutrophils, and platelets cooperate to initiate and propagate venous thrombosis in mice in vivo.

von Brühl ML, Stark K, Steinhart A, Chandraratne S, Konrad I, Lorenz M, Khandoga A, Tirniceriu A, Coletti R, Köllnberger M, Byrne RA, Laitinen I, Walch A, Brill A, Pfeiler S, Manukyan D, Braun S, Lange P, Riegger J, Ware J, Eckart A, Haidari S, Rudelius M, Schulz C, Echtler K, Brinkmann V, Schwaiger M, Preissner KT, Wagner DD, Mackman N, Engelmann B, Massberg S.

J Exp Med. 2012 Apr 9;209(4):819-35. doi: 10.1084/jem.20112322. Epub 2012 Mar 26.

 

Platelets contribute to postnatal occlusion of the ductus arteriosus.

Echtler K, Stark K, Lorenz M, Kerstan S, Walch A, Jennen L, Rudelius M, Seidl S, Kremmer E, Emambokus NR, von Bruehl ML, Frampton J, Isermann B, Genzel-Boroviczény O, Schreiber C, Mehilli J, Kastrati A, Schwaiger M, Shivdasani RA, Massberg S.

Nat Med. 2010 Jan;16(1):75-82. doi: 10.1038/nm.2060. Epub 2009 Dec 6.