eRapport

Novel therapeutic concepts in thrombosis.

Prosjekt
Prosjektnummer
2013114
Ansvarlig person
Sandip Kanse
Institusjon
Oslo universitetssykehus HF
Prosjektkategori
Åpen prosjektstøtte
Helsekategori
Stroke
Forskningsaktivitet
5. Treatment Developement
Rapporter
2018 - sluttrapport
1. We have discovered that fibrinogen is a substrate for FSAP. Fibrinogen is a key protein in the coagulation and fibrinolysis cascade as well as in important factors in regulating inflammation. The one activity of fibrinogen that was strongly influenced by FSAP was its lysis in the presence of tPA/ plasminogen. This could be important in thrombolysis in the treatment of stroke or acute myocardial infarction. (Published) 2. Using phage display we have developed a synthetic peptide that can activate pro-FSAP in human plasma. This FSAP activating peptide can be used to increase FSAP activity in plasma and in turn stimulate thrombolysis as described under point 1. (Unpublished) 3. We are currently investigating these hypotheses in mouse models of stroke Ischemic stroke is a debilitating disease with limited treatment possibilities. Clots in the blood vessels of the brain cause death of brain tissue. The current treatment used to lyse/ bust clots or remove clots is inadequate. Human genetic studies and investigations on mouse models indicate that FSAP is a key factor in the pathogenesis of stroke. Further research is in progress to determine if FSAP can improve thrombolysis. This could have a impact on the treatment of ischemic stroke patients.
2017
The goal of the project is to characterize the role of factor VII activating protease (FSAP) in thrombosis and haemsotasis and develop new therapeutic concepts based on this. The key advancements we have made this year were presented at the International Society of the Thrombosis and Haemsostasis (ISTH) Meeting in Berlin in July 2017.Presentations from this project at the International Society of the Thrombosis and Haemsostasis (ISTH) Meeting in Berlin in July 2017. Projects relating to 1, 3 and 7 are already published. For the rest, manuscripts are in prepartion. 1. Factor VII activating protease (FSAP) regulates the expression of inflammatory genes in vascular smooth muscle and endothelial cells. Kristina Byskov1, Thomas Boettger2, Paul F. Ruehle3, Nis Valentin Nielsen1, Michael Etscheid4, Sandip M. Kanse1. 1University of Oslo, Oslo, Norway. 2Max Planck Institute, Bad Nauheim, Germany. 3Friedrich Alexander University, Erlangen-Nuerenberg, Germany. 4Paul Ehrlich Institute, Langen, Germany. 2. Protease Activated Receptor-2 serves as a Receptor for Factor VII Activating Protease. Kristina Byskov1, Eric Camerer2, Sandip Kanse1. 1University of Oslo, Norway. 2INSERM U970, Paris, France 3. Analysis of the substrate specificity of Factor VII activating protease (FSAP) and design of a specific synthetic substrate. Emrah Kara1, Dipankar Manna1, Geir Åge Løset2, Eric L. Schneider3, Charles Craik3, Sandip M. Kanse1. 1Institute of Basic Medical Sciences 2Centre for Immune Regulation and Department of Biosciences, University of Oslo, Norway. 3University of California, San Francisco, USA. 4. Identification of a novel Factor VII activating protease (FSAP) zymogen-activating peptide by phage display. Sebastian Seidl1, Geir Åge Løset2, 3, Nis Valentin Nielsen1, Sandip M. Kanse1. 1Oslo University Hospital and University of Oslo, Oslo, Norway. 2Nextera, Oslo, Norway, 3Centre for Immune Regulation and Department of Biosciences, University of Oslo, Norway 5. The Factor VII Activating Protease (FSAP) accelerates fibrinolysis by altering fibrin clot structure. Michael Etscheid1, Saravanan Subramaniam2, Guenther Lochnit3, Michael Zabczyk4, Anetta Undas4 and Sandip. M. Kanse5 1Paul Ehrlich Institute, Langen, Germany. 2 University of North Carolina, Chapel Hill, USA 3Justus Liebig University, Giessen, Germany. 4Jagiellonian University Medical College, Kraków, Poland. 5University of Olso, Norway. 6. Genome-wide analysis of genetic determinants of Factor VII activating protein (FSAP) activity. Maja Olsson1, Tara M. Stanne1, Annie Pedersén1, Erik Lorentzen 1, Gunnar Engström, PhD2, Olle Melander2, Sandip M. Kanse3, Christina Jern1. 1The Sahlgrenska Academy at the University of Gothenburg, Sweden. 2Lund University, Sweden. 3University of Olso, Norway. 7. Interaction of Factor Seven Activating Protease (FSAP) with Neutrophil Extracellular Traps (NETs). Simona Grasso1, Ariane Neumann2, Maren von Koeckritz-Blickwede2, Sandip M. Kanse1 1University of Oslo, Olso, Norway. 2Department of Physiological Chemistry, University of Veterinary Medicine Hannover, Hannover, Germany. 8. Structure function analysis of Factor Seven Activating Protease (FSAP) a protease in vascular biology. Nis Valentin Nielsen1, Jens Preben Morth2, Elfie Roedel3 and Sandip M. Kanse4 1Institute of Basic Medical Sciences, 2Centre for Molecular Medicine, University of Olso, Norway. 3Promocell, Heidelberg, Germany
2016
We have characterized the role of Factor VII activating protease (FSAP) in various mouse models such as neointima formation and arteriogenesis. Phage display technique was used to develop a peptide-based activator of FSAP zymogen as well as a specific substrate for FSAP. The effect of FSAP on the phenotype of vascular cells was characterized.Following publication is accepted and in press: Factor VII activating protease (FSAP) influences vascular remodeling in the mouse hind limb ischemia model. Joerg Herold, Steven Nowak, Sawa Kostin, Jan-Marcus Daniel, Alexander Francke, Saravanan Subramaniam, Ruediger. C. Braun-Dullaeus, Sandip M. Kanse. American Journal of Translational Medicine (2017). Following three manuscripts have been submitted: 1. Identification of a novel Factor VII activating protease (FSAP) zymogen-activating peptide by phage display. Sebastian Seidl, Geir Åge Løset, Nis Valentin Nielsen, Paul J. Declerck, Sandip M. Kanse Journal of Biological Chemistry. 2. Analysis of the substrate specificity of Factor VII activating protease (FSAP) and design of a specific and sensitive peptide substrate. Emrah Kara, Dipankar Manna, Geir Åge Løset, Eric L. Schneider, Charles S. Craik, Sandip M. Kanse. Thrombosis and Haemostasis. 3. Factor VII activating protease (FSAP) regulates the expression of inflammatory genes in vascular smooth muscle and endothelial cells. Kristina Byskov, Thomas Boettger, Paul F. Ruehle, Nis Valentin Nielsen, Michael Etscheid, Sandip M. Kanse Atherosclerosis Thrombosis and Vascular Biology. Following PhD thesis is under completion and will be submitted in 2017: Emrah Kara: Characterization of the substrate specificity of FSAP using phage display. Following nine abstracts have been submitted to the International Society of Thrombosis and Hemostasis (ISTH) meeting in Berlin (July 2017) 1. NETs, FSAP and their complicity in the context of immunity and thrombosis Simona Grasso, Ariane Neumann, Maren von Köckritz-Blickwede, Sandip M. Kanse 2. Protease Activated Receptor-2 (PAR-2) serves as a dominant receptor for Factor VII Activating Protease (FSAP) Kristina Byskov and Sandip M. Kanse 3. Factor VII activating Protease (FSAP) and Marburg I (G534E), how one amino acid determines function. Nis Valentin Nielsen, Dipankar Manna, Elfie Roedel, Jens Preben Morth and Sandip Kanse 4. The Factor VII Activating Protease (FSAP) accelerates fibrinolysis by altering fibrin clot structure M. Etscheid, S. Subramaniam, G. Lochnit, M. Zabczyk, K.-M. Hanschmann, A. Undas, S. Kanse 5. A novel hypoxia response element regulates oxygen-related repression of tissue factor pathway inhibitor in breast cancer. Xue Yan Cui, Grethe Skretting, Mari Tinholt, Benedicte Stavik, Anders Erik Astrup Dahm, Sandip Kanse, Nina Iversen and Per Morten Sandset 6. Exome enriched genome-wide association analysis identifies novel influence from the ADCY2 locus on circulating levels of Factor VII activating protein (FSAP) activity Maja Olsson, Tara M. Stanne, Annie Pedersén, Erik Lorentzen, Emrah Kara, Adoracion Martinez-Palacian, Gunnar Engström, Olle Melander, Sandip M. Kanse, Christina Jern. 7. Identification of a novel Factor VII activating protease (FSAP) zymogen-activating peptide by phage display. Sebastian Seidl, Geir Åge Løset, Nis Valentin Nielsen, Paul J. Declerck, Sandip M. Kanse 8. Analysis of the substrate specificity of Factor VII activating protease (FSAP) and design of a specific and sensitive peptide substrate. Emrah Kara, Dipankar Manna, Geir Åge Løset, Eric L. Schneider, Charles S. Craik, Sandip M. Kanse. 9. Factor VII activating protease (FSAP) regulates the expression of inflammatory genes in vascular smooth muscle and endothelial cells. Kristina Byskov, Thomas Boettger, Paul F. Ruehle, Nis Valentin Nielsen, Michael Etscheid, Sandip M. Kanse
2015
FSAP knock out mice were protected against thrombosis but the outcome of stroke was worse. These are somewhat contradictory outcomes and indicate that FSAP has multiple roles in vivo. Further studies are in progress to define the molecular mechanisms involved which will help us to better understand the relationship between thrombosis and stroke.Stroke, heart attack and thrombosis are among our most frequent causes of death and disability. One in twenty Europeans has a mutated variant of the FSAP-gene which makes them more prone to these diseases. Learning more about the gene could reveal new ways to address these big global health challenges. Blood coagulation is a complex process that is in a delicate balance resulting in blood with just the right properties. Too strong a coagulation response can lead to thrombosis and too weak a coagulation response can lead to hemophilia. Our results show that FSAP seems to promote coagulation in response to tissue injury; thus, switching off the gene could lead to protection against thrombosis (Subramaniam et al, 2015, Thrombosis and Haemostasis). We have recently discovered that FSAP also changes the structure of fibrinogen and makes the clots more susceptible to fibrinolysis. This, mechanism would suggest that FSAP would protect against thrombosis. Although this mechanism seems to work in humans this does not seem to be the case in mice since we did not observe any changes in mouse fibrinogen upon switching off the mouse FSAP gene (Etscheid et al, 2016, submitted). With respect to stroke we found something quite to the contrary; switching off the gene made the consequences of stroke much worse in these mice. It seems that FSAP also protects brain cells against cell damage due to stroke. Currently we are investigating which receptors are involved in the "cytoprotective" actions of FSAP. One hot tip is that these may be G-protein coupled receptors from the family of protease activated receptors (PARs). These receptors respond to proteases from the coagulation pathway and may also be activated by FSAP. Thus FSAP seems to have good and bad properties and currently we are engaged in finding ways to "dissect" the molecule" to find out where the good and the bad parts are. For this we are trying to crystallize FSAP and define its structure at an atomic level. With this crystal structure we may be able to distinguish between the good and the bad parts of FSAP are and try to change them accordingly. In another approach is we are using a method to screen lots of different peptides for their ability to activate or inactivate FSAP. This alternative method will also provide means to "dissect" the good and bad functions of FSAP and provide tools for future studies. Artificial surfaces play an important role in medicine since they are often implanted into the body or come into contact with blood during complex surgical procedures. One problem encountered during these interventions is that blood coagulation needs to be regulated in just the right way. The accepted paradigm is that negatively charged surfaces should not be used since these are very pro-coagulant and that positively charged surfaces might be preferable. We discovered that on certain positively charged surfaces there is a strong activation of FSAP and coagulation and this has implications for design of blood-compatible surfaces (Sperling et al, 2016, Submitted). Finally, we were part of a large consortium to study the susceptibility of stroke at the whole genome level. We found that a polymorphim near the FSAP-encoding gene increases the susceptibility to stroke in the young (Cheng et al, 2016, Stroke). Further work is required to fit these pieces of the "puzzle" in a better way for the benefit of patients.
2014
FSAP is an extracellular circulating serine protease thought to be involved in the regulation of haemostasis, inflammation and tissue remodeling. Using mice lacking endogenous FSAP we demonstrate, for the first time, an important function for this factor in maintaining the balance between protective and harmful pathways in thrombosis and stroke.About 5% of Europeans are carriers of a variant of the FSAP-encoding gene that has been associated with an increased risk for stroke. However, similar studies measuring the risk of venous thrombosis did not show any conclusive link to this FSAP variant. These carriers also show a higher degree of carotid stenosis, which leads to the narrowing of the arteries in the brain. Thrombosis is a key precipitating event in a vast majority of the patients with stroke. This disease-causing variant of the enzyme has no enzymatic activity and thus we hypothesize that FSAP could be a protective factor in stroke. Understanding the pathway of how this protein influences stroke could be of tremendous diagnostic and therapeutic use. Mouse models of thrombosis and stroke can be used to mimic human disease in a realistic way and we have performed such experiments on mice with a deletion of the FSAP gene. This work was performed by Amit Joshi and Saravanan Subramaniam as part of their PhD project and has recently resulted in two publications. In a mouse model of ischemic stroke the outcome of stroke was worse in mice that lacked the FSAP gene. This was related to increased inflammation and apoptosis in the infarcted brain regions suggesting that endogenous FSAP is protective in stroke. These results were further consolidated by the findings that FSAP could protect astrocytes and neurons against cytotoxic stimuli normally found in the stroke regions of the brain. In a mouse model of thrombosis, mice lacking the FSAP gene were protected against thrombosis. A fine balance between coagulation factors and their inhibitors is very important in inhibiting thrombosis and FSAP can tilt this in favor of thrombosis. It is surprising that the two activities of FSAP are seemingly counterintuitive to each other and further studies are required to unravel these pathways. Based on our research we propose the following scenario; after stroke, tissue injury releases nuclear components such as histones and DNA that bind to and activate FSAP in the circulation. At the site of injury this activated FSAP in turn can promote blood coagulation but also protect the brain cells against various injury-causing factors found there. These fascinating in vivo findings provide us with a strong motivation to further explore the diagnostic potential of FSAP in thrombosis and stroke.
2013
The recruitment of the three people who are employed on this project was complete in August, October and November. Thus the experimental work relating the project has started but there are no results yet.Disturbance of the haemostasis system at the molecular and cellular level is involved in the pathogenesis of conditions such as myocardial infarction, stroke, venous thromboembolism (VTE), hemophilia, cancer and sepsis. The primary function of the haemostasis system is to defend the host against excessive blood loss and contribute to innate immunity by neutralizing invading microorganisms as well as participate in the wound healing response. An understanding of the mechanisms involved in arterial and venous thrombosis has had a tremendous positive impact on reducing the mortality and morbidity and traditional effective ways of controlling thrombosis include heparins, vitamin K antagonists, anti-platelet drugs and more recently direct inhibitors of coagulation factors. Especially, venous thrombosis, which is ranked 3rd amongst vascular diseases after stroke and acute myocardial infarction, remains an area with high potential for improvements. Genetic evidence from human population studies, experiments on genetically manipulated mice and in vitro investigations indicate that a protein called factor seven activating protease (FSAP) encoded by the hyaluronic acid binding protein-2 (HABP-2) gene may plays a pivotal role in thrombosis. Based on our recent discovery that FSAP inhibits tissue factor pathway inhibitor (TFPI), the major inhibitor of coagulation, we hypothesize that this interaction is involved in thrombosis. In the planned project we intend to develop this concept further and improve the currently available diagnostic and therapeutic possibilities with further research on FSAP.
Vitenskapelige artikler
Subramaniam S, Kanse SM, Kothari H, Reinhardt C, Fletcher C

Post-transcriptional, post-translational and pharmacological regulation of tissue factor pathway inhibitor.

Blood Coagul Fibrinolysis 2018 Dec;29(8):668-682.

PMID: 30439766

Cole JW, Xu H, Ryan K, Jaworek T, Dueker N, McArdle P, Gaynor B, Cheng YC, O'Connell J, Bevan S, Malik R, Ahmed NU, Amouyel P, Anjum S, Bis JC, Crosslin D, Danesh J, Engelter ST, Fornage M, Frossard P, Gieger C, Giese AK, Grond-Ginsbach C, Ho WK, Holliday E, Hopewell J, Hussain M, Iqbal W, Jabeen S, Jannes J, Kamal A, Kamatani Y, Kanse S, Kloss M, Lathrop M, Leys D, Lindgren A, Longstreth WT, Mahmood K, Meisinger C, Metso TM, Mosley T, Müller-Nurasyid M, Norrving B, Parati E, Peters A, Pezzini A, Quereshi I, Rasheed A, Rauf A, Salam T, Shen J, Slowik A, Stanne T, Strauch K, Tatlisumak T, Thijs VN, Tiedt S, Traylor M, Waldenberger M, Walters M, Zhao W, Boncoraglio G, Debette S, Jern C, Levi C, Markus H, Meschia J, Rolfs A, Rothwell P, Saleheen D, Seshadri S, Sharma P, Sudlow C, Worrall B, , , Stine OC, Kittner SJ, Mitchell BD

Genetics of the thrombomodulin-endothelial cell protein C receptor system and the risk of early-onset ischemic stroke.

PLoS One 2018;13(11):e0206554. Epub 2018 nov 1

PMID: 30383853

Etscheid M, Subramaniam S, Lochnit G, Zabczyk M, Undas A, Lang IM, Hanschmann KM, Kanse SM

Altered structure and function of fibrinogen after cleavage by Factor VII Activating Protease (FSAP).

Biochim Biophys Acta Mol Basis Dis 2018 Oct;1864(10):3397-3406. Epub 2018 aug 1

PMID: 30076961

Olsson M, Stanne TM, Pedersen A, Lorentzen E, Kara E, Martinez-Palacian A, Rønnow Sand NP, Jacobsen AF, Sandset PM, Sidelmann JJ, Engström G, Melander O, Kanse SM, Jern C

Genome-wide analysis of genetic determinants of circulating factor VII-activating protease (FSAP) activity.

J Thromb Haemost 2018 Oct;16(10):2024-2034. Epub 2018 aug 24

PMID: 30070759

Praetner M, Zuchtriegel G, Holzer M, Uhl B, Schaubächer J, Mittmann L, Fabritius M, Fürst R, Zahler S, Funken D, Lerchenberger M, Khandoga A, Kanse S, Lauber K, Krombach F, Reichel CA

Plasminogen Activator Inhibitor-1 Promotes Neutrophil Infiltration and Tissue Injury on Ischemia-Reperfusion.

Arterioscler Thromb Vasc Biol 2018 04;38(4):829-842. Epub 2018 jan 25

PMID: 29371242

Grasso S, Neumann A, Lang IM, Etscheid M, von Köckritz-Blickwede M, Kanse SM

Interaction of factor VII activating protease (FSAP) with neutrophil extracellular traps (NETs).

Thromb Res 2018 01;161():36-42. Epub 2017 nov 21

PMID: 29178989

Sperling C, Maitz MF, Grasso S, Werner C, Kanse SM

A Positively Charged Surface Triggers Coagulation Activation Through Factor VII Activating Protease (FSAP).

ACS Appl Mater Interfaces 2017 Nov 22;9(46):40107-40116. Epub 2017 nov 9

PMID: 29091393

Byskov K, Boettger T, Ruehle PF, Nielsen NV, Etscheid M, Kanse SM

Factor VII activating protease (FSAP) regulates the expression of inflammatory genes in vascular smooth muscle and endothelial cells.

Atherosclerosis 2017 Oct;265():133-139. Epub 2017 aug 25

PMID: 28881271

Cui XY, Skretting G, Tinholt M, Stavik B, Dahm AEA, Sahlberg KK, Kanse S, Iversen N, Sandset PM

A novel hypoxia response element regulates oxygen-related repression of tissue factor pathway inhibitor in the breast cancer cell line MCF-7.

Thromb Res 2017 Sep;157():111-116. Epub 2017 jul 14

PMID: 28734156

Kara E, Manna D, Løset GÅ, Schneider EL, Craik CS, Kanse S

Analysis of the substrate specificity of Factor VII activating protease (FSAP) and design of specific and sensitive peptide substrates.

Thromb Haemost 2017 Aug 30;117(9):1750-1760. Epub 2017 jul 20

PMID: 28726978

Espada S, Stavik B, Holm S, Sagen EL, Bjerkeli V, Skjelland M, Dahl TB, Espevik T, Kanse S, Sandset PM, Skretting G, Halvorsen B

Tissue factor pathway inhibitor attenuates ER stress-induced inflammation in human M2-polarized macrophages.

Biochem Biophys Res Commun 2017 09 16;491(2):442-448. Epub 2017 jul 13

PMID: 28712870

Herold J, Nowak S, Kostin S, Daniel JM, Francke A, Subramaniam S, Braun-Dullaeus RC, Kanse SM

Factor VII activating protease (FSAP) influences vascular remodeling in the mouse hind limb ischemia model.

Am J Transl Res 2017;9(6):3084-3095. Epub 2017 jun 15

PMID: 28670395

Reiterer V, Figueras-Puig C, Le Guerroue F, Confalonieri S, Vecchi M, Jalapothu D, Kanse SM, Deshaies RJ, Di Fiore PP, Behrends C, Farhan H

The pseudophosphatase STYX targets the F-box of FBXW7 and inhibits SCFFBXW7 function.

EMBO J 2017 Feb 01;36(3):260-273. Epub 2016 des 22

PMID: 28007894

Chillo O, Kleinert EC, Lautz T, Lasch M, Pagel JI, Heun Y, Troidl K, Fischer S, Caballero-Martinez A, Mauer A, Kurz AR, Assmann G, Rehberg M, Kanse SM, Nieswandt B, Walzog B, Reichel CA, Mannell H, Preissner KT, Deindl E

Perivascular Mast Cells Govern Shear Stress-Induced Arteriogenesis by Orchestrating Leukocyte Function.

Cell Rep 2016 Aug 23;16(8):2197-207. Epub 2016 aug 11

PMID: 27524614

Daniel JM, Reichel CA, Schmidt-Woell T, Dutzmann J, Zuchtriegel G, Krombach F, Herold J, Bauersachs J, Sedding DG, Kanse SM

Factor VII-activating protease deficiency promotes neointima formation by enhancing leukocyte accumulation.

J Thromb Haemost 2016 Oct;14(10):2058-2067. Epub 2016 sep 7

PMID: 27431088

Leiting S, Seidl S, Martinez-Palacian A, Muhl L, Kanse SM

Transforming Growth Factor-ß (TGF-ß) Inhibits the Expression of Factor VII-activating Protease (FSAP) in Hepatocytes.

J Biol Chem 2016 Sep 30;291(40):21020-21028. Epub 2016 jul 26

PMID: 27462075

Bustamante A, Díaz-Fernández B, Giralt D, Boned S, Pagola J, Molina CA, García-Berrocoso T, Kanse SM, Montaner J

Factor seven activating protease (FSAP) predicts response to intravenous thrombolysis in acute ischemic stroke.

Int J Stroke 2016 Aug;11(6):646-55. Epub 2016 apr 12

PMID: 27073188

Cheng YC, Stanne TM, Giese AK, Ho WK, Traylor M, Amouyel P, Holliday EG, Malik R, Xu H, Kittner SJ, Cole JW, O'Connell JR, Danesh J, Rasheed A, Zhao W, Engelter S, Grond-Ginsbach C, Kamatani Y, Lathrop M, Leys D, Thijs V, Metso TM, Tatlisumak T, Pezzini A, Parati EA, Norrving B, Bevan S, Rothwell PM, Sudlow C, Slowik A, Lindgren A, Walters MR, , Jannes J, Shen J, Crosslin D, Doheny K, Laurie CC, Kanse SM, Bis JC, Fornage M, Mosley TH, Hopewell JC, Strauch K, Müller-Nurasyid M, Gieger C, Waldenberger M, Peters A, Meisinger C, Ikram MA, Longstreth WT, Meschia JF, Seshadri S, Sharma P, Worrall B, Jern C, Levi C, Dichgans M, Boncoraglio GB, Markus HS, Debette S, Rolfs A, Saleheen D, Mitchell BD

Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2.

Stroke 2016 Feb;47(2):307-16. Epub 2016 jan 5

PMID: 26732560

Cui XY, Tinholt M, Stavik B, Dahm AE, Kanse S, Jin Y, Seidl S, Sahlberg KK, Iversen N, Skretting G, Sandset PM

Effect of hypoxia on tissue factor pathway inhibitor expression in breast cancer.

J Thromb Haemost 2016 Feb;14(2):387-96. Epub 2016 jan 30

PMID: 26598923

Reichel CA, Hessenauer ME, Pflieger K, Rehberg M, Kanse SM, Zahler S, Krombach F, Berghaus A, Strieth S

Components of the plasminogen activation system promote engraftment of porous polyethylene biomaterial via common and distinct effects.

PLoS One 2015;10(2):e0116883. Epub 2015 feb 6

PMID: 25658820

Subramaniam S, Thielmann I, Morowski M, Pragst I, Sandset PM, Nieswandt B, Etscheid M, Kanse SM

Defective thrombus formation in mice lacking endogenous factor VII activating protease (FSAP).

Thromb Haemost 2015 Apr;113(4):870-80. Epub 2014 nov 27

PMID: 25427855

Joshi AU, Orset C, Engelhardt B, Baumgart-Vogt E, Gerriets T, Vivien D, Kanse SM

Deficiency of Factor VII activating protease alters the outcome of ischemic stroke in mice.

Eur J Neurosci 2015 Apr;41(7):965-75. Epub 2015 jan 23

PMID: 25615590

Parahuleva Mariana S, Maj Robert, Hölschermann Hans, Parviz Behnoush, Abdallah Yaser, Erdogan Ali, Tillmanns Harald, Kanse Sandip M

Regulation of monocyte/macrophage function by factor VII activating protease (FSAP).

Atherosclerosis 2013 Oct;230(2):365-72. Epub 2013 aug 16

PMID: 24075769

Parahuleva Mariana S, Kanse Sandip, Hölschermann Hans, Zheleva Kirila, Zandt Daniel, Worsch Michael, Parviz Behnoush, Güttler Norbert, Tillmanns Harald, Böning Andreas, Erdogan Ali

Association of circulating factor seven activating protease (FSAP) and of oral Omega-3 fatty acids supplements with clinical outcome in patients with atrial fibrillation: the OMEGA-AF study.

J Thromb Thrombolysis 2013 Apr 11. Epub 2013 apr 11

PMID: 23575879

Doktorgrader
Emrah Kara

Identifying Factor VII activating protease (FSAP) substrate specificity by phage display

Disputert:
november 2018
Hovedveileder:
Sandip Kanse
Amit Joshi

The pathophysiological significance of Factor VII activating protease (FSAP) in ischemic stroke

Disputert:
juni 2014
Hovedveileder:
Sandip Kanse
Saravanan Subramaniam

Factor VII activating protease (FSAP) in thrombosis and haemostasis in vivo

Disputert:
september 2014
Hovedveileder:
Sandip Kanse
Deltagere
  • Sandip Kanse Prosjektleder
  • Sebastian Seidl Postdoktorstipendiat (finansiert av denne bevilgning)
  • Sandra Espada Serrano Postdoktorstipendiat (finansiert av denne bevilgning)
  • Emrah Kara Doktorgradsstipendiat (finansiert av denne bevilgning)
  • Sebastian Seidl Postdoktorstipendiat
  • Sandip Kanse Prosjektleder

eRapport er utarbeidet av Sølvi Lerfald og Reidar Thorstensen, Regionalt kompetansesenter for klinisk forskning, Helse Vest RHF, og videreutvikles av de fire RHF-ene i fellesskap, med støtte fra Helse Vest IKT

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