Visual Universitätsmedizin Mainz

Professorship "Vascular Inflammation"

Prof. Philip Wenzel, MD

Proinflammatory Lysozyme M (LysM) positive CD11b+Gr-1+ monocytes, vascular macrophages and  CD11b+Gr-1+ neutrophils are mediators of ATII-induced vascular dysfunction and are essential for development of arterial hypertension. In the DFG project WE 4361/3-1, we persue the research topic of inflammatory myelomonocytic cells in arterial hypertension.

There is cumulating evidence, that LysM+ cells are causally involved in venous thrombus formation and embolism (VTE), and that pulmonary hypertension is paralelled or even partially mediated by inflammatory macrophages in the pulmonary vasculature. In the project IRBA2, the PhD student Melanie Schwenk mentored by Christian Becker is currently working on the role of inflammatory lymphocytes in arterial and venous thrombosis. In conjunction with these topics, additional studies in vascular biology delicated to the impact of coagulation factors of the contact phase system on vascular dysfunction will be continued.

We will use the technique of inducible ablation of inflammatory myeloid cells to study mechanisms of venous and arterial thrombosis in the mouse models of vena cava ligation and LAD-ligation.

Research interests

  • Role of inflammatory myelomonocytic cells in vascular dysfunction and venous and arterial thrombosis

  • Proinflammatory Cytokines and activation of inflammatory pathways in vascular biology

  • Interplay of coagulation factors, leukocytes and platelets in vascular dysfunction

Partners of Collaboration

  • PD Christian Becker, PhD (Dermatology, University Medical Center Mainz)

  • Professor Ari Waisman, PhD (Institute of Molecular Medicine, University Medical Center Mainz)

  • Christoph Reinhardt, PhD (CTH, University Medical Center Mainz)

  • George Reid, PhD (Institute for Molecular Biology, JGU Mainz)
  • Professor Wolfram Ruf, MD (Scripps Institute, La Jolla, USA)
  • Professor Thomas Renné, MD, PhD (Karolinska Institutet, Stockholm)

Research Funding

  • CTH TRP X12
  • Boehringer Ingelheim
  • Foundation of Pathobiochemistry and Molecular Diagnostics
  • MAIFOR
  • DFG WE 4361/3-1
  • DFG WE 4361/4-1
  • DZHK

Team - Professorship 'Vascular Inflammation'

Wenzel, MD
Professor Philip Wenzel, MD
Position: Professorship 'Vascular Inflammation', Physician Cardiology I, DZHK Scientist

06131/17-7695
wenzelp@uni-mainz.de

Karbach, MD
Susanne Karbach, MD
Position: Physician Cardiology I, Scientist

karbasu@uni-mainz.de
Further Information

Brandt, MD
Jan Moritz Brandt, MD
Position: Physician Cardiology I, Virchow-Fellow

brandtmo@uni-mainz.de
Further Information

Conze
Anne-Kristin Conze
Position: Technical assistant

06131/17-8034
Anne-Kristin.Conze@unimedizin-mainz.de

Dörschmann
Hendrik Dörschmann
Position: PhD student

06131/17-8036
h.doerschmann@uni-mainz.de

PhD Finger
Stefanie Finger, PhD
Position: Lab manager

Stefanie.Finger@unimedizin-mainz.de

Garlapati
Venkata Subbaiah Garlapati
Position: Graduate student

06131/17-8036
garlapati.venkatasubbaiah@unimedizin-mainz.de

Perius
Katharina Perius
Position: Technician

06131/17-8034
06131/17-8047

Virchow Fellow

MD Molitor
Michael Molitor, MD
Position: Physician Cardiology I
Virchow Fellow, CTH

06131/17-8036
micmolit@uni-mainz.de

Research stay abroad

Kossmann, PhD
Sabine Kossmann, PhD
Position: Postdoctoral Researcher at Heart Research Institute, University of Sydney
www.hri.org.au
Virchow Fellow

sabine.kossmann@hri.org.au
Further Information

Former team members

  • Anja Conrad, tec (Max-Delbrück-Center, Berlin)
  • Isabel Schmidgen, MD, Dermatology, University Medical Center Mainz
  • Jan Stratmann, MD, Clinic for Haematology and Oncology, University Medical Center Frankfurt
  • Daniel Minwegen, MD Neurology, University Mediacal Center Göttingen
  • Tanja Schönfelder, DVM, Max-Planck-Forschungsstelle für Neurogenetik, Frankfurt a. M. 
  • Eleni Giokoglu, MD, Clinic for Cardiology, University Medical Center Frankfurt

Reviews

  • Karbach S, Lagrange J, Wenzel P. Thromboinflammation and Vascular Dysfunction. Hamostaseologie 2018.
  • Lagrange J, Wenzel P. The regulatory role of coagulation factors in vascular function. Front Biosci (Landmark Ed) 2019;24:494-513.
  • Wenzel P. Monocytes as immune targets in arterial hypertension. Br J Pharmacol 2019;176(12):1966-1977.
  • Carnevale D, Wenzel P. Mechanical stretch on endothelial cells interconnects innate and adaptive immune response in hypertension. Cardiovasc Res 2018.
  • Schönfelder T, Jäckel S, Wenzel P (2017) Mouse models of deep vein thrombosis. Gefasschirurgie 22: 28-33
  • Lagrange J, Kossmann S, Wenzel P (2017) Assessment of Vascular Dysfunction and Inflammation Induced by Angiotensin II in Mice. Methods Mol Biol 1559: 439-453
  • Wenzel P, Kossmann S, Münzel T, Daiber A (2017) Redox regulation of cardiovascular inflammation - Immunomodulatory function of mitochondrial and Nox-derived reactive oxygen and nitrogen species. Free Radic Biol Med 109: 48-60
  • Knorr M, Münzel T, Wenzel P. Interplay of NK cells and monocytes in vascular inflammation and myocardial infarction. Frontiers in physiology. 5:295, 2014.

Original articles

  • Brandt M, Giokoglu E, Garlapati V, Bochenek ML, Molitor M, Hobohm L, Schönfelder T, Münzel T, Kossmann S, Karbach SH, Schäfer K, Wenzel P. Pulmonary Arterial Hypertension and Endothelial Dysfunction Is Linked to NADPH Oxidase-Derived Superoxide Formation in Venous Thrombosis and Pulmonary Embolism in Mice. Oxid Med Cell Longev 2018;2018:1860513.
  • Jansen T, Kröller-Schön S, Schönfelder T, Foretz M, Viollet B, Daiber A, Oelze M, Brandt M, Steven S, Kvandova M, Kalinovic S, Lagrange J, Keaney JF, Jr., Münzel T, Wenzel P, Schulz E. alpha1AMPK deletion in myelomonocytic cells induces a pro-inflammatory phenotype and enhances angiotensin II-induced vascular dysfunction. Cardiovasc Res 2018;114(14):1883-1893.
  • Gogiraju R, Hubert A, Fahrer J, Straub BK, Brandt M, Wenzel P, Münzel T, Konstantinides S, Hasenfuss G, Schäfer K. Endothelial Leptin Receptor Deletion Promotes Cardiac Autophagy and Angiogenesis Following Pressure Overload by Suppressing Akt/mTOR Signaling. Circ Heart Fail 2019;12(1):e005622.
  • Kiouptsi K, Finger S, Garlapati VS, Knorr M, Brandt M, Walter U, Wenzel P, Reinhardt C. Hypoxia evokes increased PDI and PDIA6 expression in the infarcted myocardium of ex-germ-free and conventionally raised mice. Biol Open 2019;8(1).
  • Kröller-Schön S, Jansen T, Tran TLP, Kvandova M, Kalinovic S, Oelze M, Keaney JF, Jr., Foretz M, Viollet B, Daiber A, Kossmann S, Lagrange J, Frenis K, Wenzel P, Münzel T, Schulz E. Endothelial alpha1AMPK modulates angiotensin II-mediated vascular inflammation and dysfunction. Basic Res Cardiol 2019;114(2):8.
  • Schüler R, Brand A, Klebow S, Wild J, Veras FP, Ullmann E, Roohani S, Kolbinger F, Kossmann S, Wohn C, Daiber A, Münzel T, Wenzel P, Waisman A, Clausen BE, Karbach S. Antagonization of IL-17A Attenuates Skin Inflammation and Vascular Dysfunction in Mouse Models of Psoriasis. J Invest Dermatol 2019;139(3):638-647.
  • Bochenek ML, Bauer T, Gogiraju R, Nadir Y, Mann A, Schönfelder T, Hunig L, Brenner B, Münzel T, Wenzel P, Konstantinides S, Schäfer K. The endothelial tumor suppressor p53 is essential for venous thrombus formation in aged mice. Blood Adv 2018;2(11):1300-1314.
  • 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(131).
  • Schönfelder T, Brandt M, Kossmann S, Knopp T, Münzel T, Walter U, Karbach SH, Wenzel P. Lack of T-bet reduces monocytic interleukin-12 formation and accelerates thrombus resolution in deep vein thrombosis. Sci Rep 2018;8(1):3013.
  • Siegismund CS, Escher F, Lassner D, Kühl U, Gross U, Fruhwald F, Wenzel P, Münzel T, Frey N, Linke RP, Schultheiss HP. Intramyocardial inflammation predicts adverse outcome in patients with cardiac AL amyloidosis. Eur J Heart Fail 2018;20(4):751-757.
  • Sotiriou E, Heiner S, Jansen T, Brandt M, Schmidt KH, Kreitner KF, Emrich T, Schultheiss HP, Schulz E, Münzel T, Wenzel P. Therapeutic implications of a combined diagnostic workup including endomyocardial biopsy in an all-comer population of patients with heart failure: a retrospective analysis. ESC Heart Fail 2018.
  • 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  (2017) Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension. Sci Transl Med 9

  • Sag CM, Schnelle M, Zhang J, Murdoch CE, Kossmann S, Protti A, Santos CXC, Sawyer G, Zhang X, Mongue-Din H, Richards DA, Brewer AC, Prysyazhna O, Maier LS, Wenzel P, Eaton PJ, Shah AM (2017) Distinct Regulatory Effects of Myeloid Cell and Endothelial Cell NAPDH Oxidase 2 on Blood Pressure. Circulation 135: 2163-2177
  • Steven S, Oelze M, Hanf A, Kröller-Schön S, Kashani F, Roohani S, Welschof P, Kopp M, Godtel-Armbrust U, Xia N, Li H, Schulz E, Lackner KJ, Wojnowski L, Bottari SP, Wenzel P, Mayoux E, Münzel T, Daiber A (2017) The SGLT2 inhibitor empagliflozin improves the primary diabetic complications in ZDF rats. Redox Biol 13: 370-385
  • Subramaniam S, Jurk K, Hobohm L, Jäckel S, Saffarzadeh M, Schwierczek K, Wenzel P, Langer F, Reinhardt C, Ruf W (2017) Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development. Blood 129: 2291-2302
  • Steven S, Oelze M, Brandt M, Ullmann E, Kröller-Schön S, Heeren T, Tran LP, Daub S, Dib M, Stalleicken D, Wenzel P, Münzel T, Daiber A (2017) Pentaerythritol Tetranitrate In Vivo Treatment Improves Oxidative Stress and Vascular Dysfunction by Suppression of Endothelin-1 Signaling in Monocrotaline-Induced Pulmonary Hypertension. Oxid Med Cell Longev 2017: 4353462
  • Steven S, Jurk K, Kopp M, Kröller-Schön S, Mikhed Y, Schwierczek K, Roohani S, Kashani F, Oelze M, Klein T, Tokalov S, Danckwardt S, Strand S, Wenzel P, Münzel T, Daiber A (2017) Glucagon-like peptide-1 receptor signalling reduces microvascular thrombosis, nitro-oxidative stress and platelet activation in endotoxaemic mice. British journal of pharmacology 174: 1620-1632
  • Brandt M, Garlapati V, Oelze M, Sotiriou E, Knorr M, Kröller-Schön S, Kossmann S, Schönfelder T, Morawietz H, Schulz E, Schultheiss HP, Daiber A, Münzel T, Wenzel P (2016) NOX2 amplifies acetaldehyde-mediated cardiomyocyte mitochondrial dysfunction in alcoholic cardiomyopathy. Scientific reports 6: 32554
  • Karbach SH, Schönfelder T, Brandao I, Wilms E, Hörmann N, Jäckel S, Schüler R, Finger SKnorr MLagrange J, Brandt M, Waisman A, Kossmann S, Schäfer K, Münzel T, Reinhardt C, Wenzel P (2016) Gut Microbiota Promote Angiotensin II-Induced Arterial Hypertension and Vascular Dysfunction. Journal of the American Heart Association 5
  • Steven S, Jurk K, Kopp M, Kröller-Schön S, Mikhed Y, Schwierczek K, Roohani S, Kashani F, Oelze M, Klein T, Tokalov S, Danckwardt S, Strand S, Wenzel P, Münzel T, Daiber A (2016) Glucagon-like peptide-1 receptor signalling reduces microvascular thrombosis, nitro-oxidative stress and platelet activation in endotoxaemic mice. British journal of pharmacology
  • Wenzel P, Rossmann H, Müller C, Kossmann S, Oelze M, Schulz A, Arnold N, Simsek C, Lagrange J, Klemz R, Schönfelder TBrandt MKarbach SH, Knorr MFinger 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. European heart journal. 2015.
  • Karbach S, Croxford AL, Oelze M, Schuler R, Minwegen D, Wegner J, Koukes L, Yogev N, Nikolaev A, Reissig S, Ullmann A, Knorr M, Waldner M, Neurath MF, Li H, Wu Z, Brochhausen C, Scheller J, Rose-John S, Piotrowski C, Bechmann I, Radsak M, Wild P, Daiber A, von Stebut E*, Wenzel P*, Waisman A*, Munzel T*. Interleukin 17 drives vascular inflammation, endothelial dysfunction, and arterial hypertension in psoriasis-like skin disease. Arteriosclerosis, thrombosis, and vascular biology. 34:2658-2668, 2014. 
  • * these authors contributed equally
  • Kossmann S, Hu H, Steven SSchönfelder T, Fraccarollo D, Mikhed Y, Brähler M, Knorr MBrandt MKarbach SHBecker C, Oelze M, Bauersachs J, Widder J, Münzel TDaiber A,Wenzel P. Inflammatory Monocytes Determine Endothelial Nitric Oxide Synthase Uncoupling and Nitro-oxidative Stress Induced by Angiotensin II. Journal of Biological Chemistry. pii: jbc.M114.604231, 2014.
  • Brandt M, Schönfelder T, Schwenk M, Becker CJäckel SReinhardt C, Stark K, Massberg S, Münzel T, von Brühl ML, Wenzel P. Deep vein thrombus formation induced by flow reduction in mice is determined by venous side branches. Clinical Hemorheology and Microcirculation. 56(2):145-5, 2014.
  • Kossmann S, Schwenk M, Hausding M, Karbach S, Schmidgen M, Brandt MKnorr M, Hu H, Kröller-Schön S, Schönfelder TGrabbe S, Oelze M, Daiber AMünzel T, Becker CWenzel P. Angiotensin II–Induced Vascular Dysfunction Depends on Interferon-γ–Driven Immune Cell Recruitment and Mutual Activation of Monocytes and NK-Cells. Arteriosclerosis, Thrombosis, and Vascular Biology. 33:1313-1319, 2013.
  • Wenzel PKnorr M, Kossmann S, Stratmann J, Hausding M, Schuhmacher S, Karbach SH, Schwenk M, Yogev N, Schulz E, Oelze M, Grabbe S, Jonuleit H, Becker C, Daiber A, Waisman A, Munzel T. Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction. Circulation. 2011; 124(12):1370-81, 2011.
  • Team 2011: PD Dr. Philip Wenzel, Dr. Maike Knorr und Kollegen, II. Med. Klinik und Poliklinik, Interview mit Philip Wenzel und Maike Knorr im Magazin "Circulation" vom 6. Dez. 2011 (Pdf-file, 997,0 KB)
Editorial Commentary

Under Pressure: A New Role for CD11c+ Myeloid Cells in Hypertension.
Kossmann S, Wenzel P.

Hypertension. 2018 Jan 29. pii: HYPERTENSIONAHA.117.10216. [Epub ahead of print]