The action of fibrin fragments in the context of vascular leak and inflammation
We are interested in the involvement of microvascular endothelial cells in inflammation and loss of vascular barrier function. Alteration in vascular permeability is most pronounced in small blood vessels. The loss of the vascular barrier function leads to migration of inflammatory cells into the tissue and in the worst case to leak of fluid and proteins into the tissue, shock and death. Endothelial cell-to-cell contacts built up by VE-cadherin, but also contacts to the extracellular matrices are keys in establishing vascular responses to stress factors, like thrombin, histamine and inflammatory cytokines. Both types of endothelial cell contacts are controlled by small GTPases and the dynamics of the cytoskeleton. We are investigating the influence of Bβ15-42 (also called FX06), a plasmin digest product of fibrin, in preventing endothelial cell permeability via the small GTPases and the src-kinase Fyn by its interaction with the VE-cadherin as well as at the focal adhesion complex.
Publications
- Bβ15-42 protects against acid-induced acute lung injury and secondary Pseudomonas pneumonia in vivo.
2009. Matt U, Warszawska JM, Bauer M,Dietl W, Mesteri I, Doninger B, Haslinger I, Schabbauer G,Perkmann T, Binder CJ, Reingruber S, Petzelbauer P and Knapp S. Am. J. Respir. Crit. Care Med. Published ahead of print on September 17 - Bbeta15-42 (FX06) reduces pulmonary, myocardial, liver, and small intestine damage in a pig model of hemorrhagic shock and reperfusion.
2009. Roesner JP, Petzelbauer P, Koch A, Tran N, Iber T, Vagts DA, Scheeren TW, Vollmar B, Nöldge-Schomburg GE, Zacharowski K.Crit care med Feb;37(2):598-605. - Peptide Bβ15-42 preserves endothelial barrier function in shock. plos ONE 4(4): e5391.
2009.Gröger M, Pasteiner W, Ignatyev G, Matt U, Knapp S, Atrasheuskaya A, Bukin E, Friedl P, Zinkl D, Hofer-Warbinek R, Zacharowski K, Petzelbauer P and Reingruber S. - Effect of intravenous FX06 as an adjunct to primary percutaneous coronary intervention for acute ST-segment elevation myocardial infarction results of the F.I.R.E. (Efficacy of FX06 in the Prevention of Myocardial Reperfusion Injury) trial.
2009. Atar D, Petzelbauer P, Schwitter J, Huber K, Rensing B, Kasprzak JD, Butter C, Grip L, Hansen PR, Süselbeck T, Clemmensen PM, Marin-Galiano M, Geudelin B, Buser PT; F.I.R.E. Investigators. J Am Coll Cardiol. Feb 24;53(8):720-9. - A double blind, single centre, sub-chronic reperfusion trial evaluating FX06 following haemorrhagic shock in pigs.
2009. Roesner JP, Petzelbauer P, Koch A, Tran N, Iber T, Mutz C, Vollmar B, Nöldge-Schomburg GE, Zacharowski K. Resuscitation.Feb;80(2):264-71. Epub 2008 Dec 5. - The fibrin-derived peptide Bbeta15-42 is cardioprotective in a pig model of myocardial ischemia-reperfusion injury.
2007. Roesner JP, Petzelbauer P, Koch A, Mersmann J, Zacharowski PA, Boehm O, Reingruber S, Pasteiner W, Mascher D, Wolzt M, Barthuber C, Nöldge-Schomburg GE, Scheeren TW, Zacharowski K. Crit Care Med. Jul;35(7):1730-5. - The fibrin-derived peptide Bbeta15-42 protects the myocardium against ischemia-reperfusion injury.
2005. Petzelbauer P, Zacharowski PA, Miyazaki Y, Friedl P, Wickenhauser G, Castellino FJ, Gröger M, Wolff K, Zacharowski K. Nat Med. Mar;11(3):298-304. Epub 2005 Feb 20. - Anti-TNF antibody treatment reduces mortality in experimental dengue virus infection.
2003. Atrasheuskaya A, Petzelbauer P, Fredeking TM, Ignatyev G. FEMS Immunol Med Microbiol. Jan 21;35(1):33-42.
