Platform 1

Intravital Microscopy

Arterial thrombosis is caused by injury of the vascular endothelium or by rupture of atherosclerotic plaques. Consequences can be myocardial infarction or stroke, these are major causes of death worldwide.

One main cause of venous thrombosis is a reduction of blood flow caused by immobility after surgery or during long flights and train journeys. Blood clots often develop in the deep vein legs (deep venous thrombosis, DVT). These clots can break off from vein walls and travel to the lungs, where they can cause a pulmonary embolism.

With the help of various mouse models in combination with intravital microscopy, thrombus formation can be visualised and thus  a real-time representation of the cellular processes in vivo possible. Various mouse thrombosis models have been established in this platform, such as the carotid artery ligation model, vena cava stenosis model and the mesenteric ischaemia-reperfusion model.

Partners using this method

Partners at the CTH

• Prof. Dr. Wolfram Ruf (Cell Signaling Pathways of the Hemostatic System)
• Prof. Dr. Philip Wenzel (Vascular Inflammation)
• Prof. Dr. Christoph Reinhardt (Experimental Hemostasis and Gnotobiotics)
  

Partners at the University Medical Center Mainz

• Prof. Dr. Katrin Schäfer (Center for Cardiology – Cardiology I)
• Prof. Andreas Daiber (II. Department of Medicine and Polyclinic - Molecular Cardiology)
• Prof. Huige Li (Institute for Pharmacology)

Platform

• This platform is part of the 'Shared Expertise' of the DZHK ('Plattformlobor CTH' - shared expertise SE076)

Scientific Platform Coordinators

References (selection)

• Kiouptsi K, Casari M, Mandel J, Gao Z, Deppermann C. Intravital Imaging of Thrombosis Models in Mice. Hamostaseologie. 2023 Oct;43(5):348-359.
• Molitor M, Bayo-Jimenez MT, Hahad O, Witzler C, Finger S, Garlapati VS, Rajlic S, Knopp T, Bieler TK, Aluia M, Wild J, Lagrange J, Blessing R, Rapp S, Schulz A, Kleinert H, Karbach S, Steven S, Ruf W, Wild P, Daiber A, Münzel T, Wenzel P. Aircraft noise exposure induces pro-inflammatory vascular conditioning and amplifies vascular dysfunction and impairment of cardiac function after myocardial infarction. Cardiovasc Res. 2023 Jun 13;119(6):1416-1426.
• Ascher S, Wilms E, Pontarollo G, Formes H, Bayer F, Müller M, Malinarich F, Grill A, Bosmann M, Saffarzadeh M, Brandão I, Groß K, Kiouptsi K, Kittner JM, Lackner KJ, Jurk K, Reinhardt C. Gut Microbiota Restricts NETosis in Acute Mesenteric Ischemia-Reperfusion Injury. Arterioscler Thromb Vasc Biol. 2020 Sep;40(9):2279-2292.
• Lagrange J, Kossmann S, Kiouptsi K, Wenzel P. Visualizing Leukocyte Rolling and Adhesion in Angiotensin II-Infused Mice: Techniques and Pitfalls. J Vis Exp. 2018 Jan 4;(131):56948.
• Jäckel S, Kiouptsi K, Lillich M, Hendrikx T, Khandagale A, Kollar B, Hörmann N, Reiss C, Subramaniam S, Wilms E, Ebner K, Brühl MV, Rausch P, Baines JF, Haberichter S, Lämmle B, Binder CJ, Jurk K, Ruggeri ZM, Massberg S, Walter U, Ruf W, Reinhardt C. Gut microbiota regulate hepatic von Willebrand factor synthesis and arterial thrombus formation via Toll-like receptor-2. Blood. 2017 Jul 27;130(4):542-553.
• Schönfelder T, Jäckel S, Wenzel P. Mouse models of deep vein thrombosis. Gefasschirurgie. 2017;22(Suppl 1):28-33.
• Kossmann S, Lagrange J, Jäckel S, Jurk K, Ehlken M, Schönfelder T, Weihert Y, Knorr M, Brandt M, Xia N, Li H, Daiber A, Oelze M, Reinhardt C, Lackner K, Gruber A, Monia B, Karbach SH, Walter U, Ruggeri ZM, Renné T, Ruf W, Münzel T, Wenzel P. Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension. Sci Transl Med. 2017 Feb 1;9(375):eaah4923.
• Müller-Calleja N, Manukyan D, Canisius A, Strand D, Lackner KJ. Hydroxychloroquine inhibits proinflammatory signalling pathways by targeting endosomal NADPH oxidase. Ann Rheum Dis. 2017 May;76(5):891-897.
• Luther N, Shahneh F, Brähler M, Krebs F, Jäckel S, Subramaniam S, Stanger C, Schönfelder T, Kleis-Fischer B, Reinhardt C, Probst HC, Wenzel P, Schäfer K, Becker C. Innate Effector-Memory T-Cell Activation Regulates Post-Thrombotic Vein Wall Inflammation and Thrombus Resolution. Circ Res. 2016 Dec 9;119(12):1286-1295.
• Manukyan D, Müller-Calleja N, Jäckel S, Luchmann K, Mönnikes R, Kiouptsi K, Reinhardt C, Jurk K, Walter U, Lackner KJ. Cofactor-independent human antiphospholipid antibodies induce venous thrombosis in mice. J Thromb Haemost. 2016 May;14(5):1011-20.
• Wenzel P, Rossmann H, Müller C, Kossmann S, Oelze M, Schulz A, Arnold N, Simsek C, Lagrange J, Klemz R, Schönfelder T, Brandt M, Karbach SH, Knorr M, Finger S, Neukirch C, Häuser F, Beutel ME, Kröller-Schön S, Schulz E, Schnabel RB, Lackner K, Wild PS, Zeller T, Daiber A, Blankenberg S, Münzel T. Heme oxygenase-1 suppresses a pro-inflammatory phenotype in monocytes and determines endothelial function and arterial hypertension in mice and humans. Eur Heart J. 2015 Dec 21;36(48):3437-46. Erratum in: Eur Heart J. 2018 Mar 14;39(11):967.