ischemia / reperfusion injury; glycocalyx; endothelial cells; complement; heparan sulfate proteoglycans; innate immunity; myocardial infarction; pigs; rats
Zhang S, Duehrkop C, Plock J A, Rieben R (2015), Inhalation anesthesia of rats: influence of the fraction of inspired oxygen on limb ischemia/reperfusion injury., in Laboratory animals
, 50(3), 185-97.
Bongoni Anjan K, Kiermeir David, Denoyelle Julie, Jenni Hansjörg, Burlak Christopher, Seebach Jörg D, Vögelin Esther, Constantinescu Mihai A, Rieben Robert (2015), Porcine extrahepatic vascular endothelial asialoglycoprotein receptor 1 mediates xenogeneic platelet phagocytosis in vitro and in human-to-pig ex vivo xenoperfusion., in Transplantation
, 99(4), 693-701.
Ahrens H E, Petersen B, Herrmann D, Lucas-Hahn A, Hassel P, Ziegler M, Kues W A, Baulain U, Baars W, Schwinzer R, Denner J, Rataj D, Werwitzke S, Tiede A, Bongoni A K, Garimella P S, Despont A, Rieben R, Niemann H (2015), siRNA mediated knockdown of tissue factor expression in pigs for xenotransplantation., in American journal of transplantation : official journal of the American Society of Transplantation an
, 15(5), 1407-14.
Bongoni Anjan K, Kiermeir David, Schnider Jonas, Jenni Hansjörg, Garimella Pavan, Bähr Andrea, Klymiuk Nikolai, Wolf Eckhard, Ayares David, Voegelin Esther, Constantinescu Mihai A, Seebach Jörg D, Rieben Robert (2015), Transgenic Expression of Human CD46 on Porcine Endothelium: Effect on Coagulation and Fibrinolytic Cascades During Ex Vivo Human-to-Pig Limb Xenoperfusions., in Transplantation
, 99(10), 2061-9.
Bongoni Anjan K., Kiermeir David, Jenni Hansjoerg, Baehr Andrea, Ayares David, Klymiuk Nikolai, Wolf Eckhard, Voegelin Esther, Constantinescu Mihai A., Seebach Jorg D., Rieben Robert (2014), Complement dependent early immunological responses during ex vivo xenoperfusion of hCD46/HLA-E double transgenic pig forelimbs with human blood, in XENOTRANSPLANTATION
, 21(3), 230-243.
Duehrkop Claudia, Rieben Robert (2014), Ischemia/reperfusion injury: Effect of simultaneous inhibition of plasma cascade systems versus specific complement inhibition, in BIOCHEMICAL PHARMACOLOGY
, 88(1), 12-22.
Duehrkop C., Rieben R. (2014), Refinement of tourniquet-induced peripheral ischemia/reperfusion injury in rats: comparison of 2 h vs 24 h reperfusion, in LABORATORY ANIMALS
, 48(2), 143-154.
Wuensch Annegret, Baehr Andrea, Bongoni Anjan K., Kemter Elisabeth, Blutke Andreas, Baars Wiebke, Haertle Sonja, Zakhartchenko Valeri, Kurome Mayuko, Kessler Barbara, Faber Claudius, Abicht Jan-Michael, Reichart Bruno, Wanke Ruediger, Schwinzer Reinhard, Nagashima Hiroshi, Rieben Robert, Ayares David, Wolf Eckhard, Klymiuk Nikolai (2014), Regulatory Sequences of the Porcine THBD Gene Facilitate Endothelial-Specific Expression of Bioactive Human Thrombomodulin in Single-and Multitransgenic Pigs, in TRANSPLANTATION
, 97(2), 138-147.
Duehrkop Claudia, Denoyelle Julie, Shaw Sidney, Rieben Robert (2014), Use of dextran sulfate in tourniquet-induced skeletal muscle reperfusion injury, in JOURNAL OF SURGICAL RESEARCH
, 187(1), 150-161.
Bongoni Anjan K., Kiermeir David, Jenni Hansjoerg, Wuensch Annegret, Baehr Andrea, Ayares David, Seebach Joerg D., Wolf Eckhard, Klymiuk Nikolai, Constantinescu Mihai A., Voegelin Esther, Rieben Robert (2013), Activation of the Lectin Pathway of Complement in Pig-to-Human Xenotransplantation Models, in TRANSPLANTATION
, 96(9), 791-799.
Duehrkop Claudia, Banz Yara, Spirig Rolf, Miescher Sylvia, Nolte Marc W., Spycher Martin, Smith Richard A. G., Sacks Steven H., Rieben Robert (2013), C1 Esterase Inhibitor Reduces Lower Extremity Ischemia/Reperfusion Injury and Associated Lung Damage, in PLOS ONE
, 8(8), e72059.
Barratt-Due Andreas, Thorgersen Ebbe B, Egge Kjetil, Pischke Søren, Sokolov Andrey, Hellerud Bernt C, Lindstad Julie K, Pharo Anne, Bongoni Anjan K, Rieben Robert, Nunn Miles, Scott Helge, Mollnes Tom E (2013), Combined Inhibition of Complement (C5) and CD14 Markedly Attenuates Inflammation, Thrombogenicity, and Hemodynamic Changes in Porcine Sepsis., in Journal of immunology (Baltimore, Md. : 1950)
Bongoni AK, Lanz J, Rieben R, Banz Y (2013), Development of a bead-based multiplex assay for the simultaneous detection of porcine inflammation markers using xMAP technology, in Cytometry Part A
, 83(7), 636-647.
Spirig Rolf, Schaub Alexander, Kropf Alain, Miescher Sylvia, Spycher Martin O., Rieben Robert (2013), Reconstituted High-Density Lipoprotein Modulates Activation of Human Leukocytes, in PLOS ONE
, 8(8), e71235.
Kamat Pranitha, Juon Bettina, Jossen Brigitte, Gajanayake Thusitha, Rieben Robert, Vögelin Esther (2012), Assessment of endothelium and inflammatory response at the onset of reperfusion injury in hand surgery., in Journal of inflammation (London, England)
, 9(1), 18-18.
Banz Yara, Hess Otto M, Meier Pascal, Korchagina Elena Y, Gordeeva Elena A, Robson Simon C, Gajanayake Thusitha, Csizmadia Eva, Mettler Daniel, Haeberli André, Bovin Nicolai V, Rieben Robert (2012), Evaluation of multimeric tyrosine-O-sulfate as a cytoprotectant in an in vivo model of acute myocardial infarction in pigs., in Cardiology
, 121(1), 59-70.
Banz Yara, Rieben Robert (2012), Role of complement and perspectives for intervention in ischemia-reperfusion damage., in Annals of medicine
, 44(3), 205-17.
Background: Activation of innate immunity is a key problem in ischemia/reperfusion (I/R) injury. Damage of endothelial cells (EC) is initiated by inflammatory mediators, among which complement plays an important role.Working Hypothesis: In I/R injury initial changes on the endothelium, probably a beginning release of the glycocalyx layer, render it susceptible to attack by mediators of innate immunity, in particular complement. The ensuing EC activation is characterized by release of Heparan Sulfate Proteoglycans (HSPG). Low molecular weight dextran sulfate (DXS) acts as an EC-protectant, attenuating further EC activation and HSPG shedding.Specific Aims:•To analyze I/R injury induced shedding of HSPG on a molecular level, and to assess binding of complement regulatory proteins to HSPG as well as DXS.•To characterize the potential of DXS, IVIG and C1-inhibitor to reduce I/R injury in a rat hind limb ischemia model.•To assess the effects of cytoprotection with DXS on infarct size and cardiac function several hours to weeks after myocardial infarction and treatmentExperimental Design: The project comprises biochemical analyses, in vitro cell culture methods and animal models with rats and pigs. As a continuation of earlier pig myocardial infarction experiments the effect of DXS on infarct size and cardiac function will be assessed up to two weeks after infarction and reperfusion.Expected Value: This project addresses key problems of the understanding of the pathophysiology of I/R injury and links basic science to clinical application. Possible applications are not limited to myocardial and peripheral I/R injury, but will include other diseases in which complement, EC and the activation of complement play a role. In addition, our investigation into I/R injury is important also in angiology, cardiovascular surgery and neurology (stroke).