Professur "Vaskuläre Inflammation"

Prof. Dr. Philip Wenzel

Gefäßentzündungen führen zu endothelialer Dysfunktion und sind ein wichtiger Faktor in der Pathophysiologie des Alterns und altersbedingter Herz-Kreislauf-Erkrankungen wie arterielle Hypertonie, koronare Herzkrankheit und Herzversagen. Es gibt viele potenzielle Angriffspunkte für Medikamente, von denen Patienten mit Herzinfarkt, venösen Thromboembolien und Ischämie-Reperfusionsschäden sowie chronischen Entzündungskrankheiten wie Psoriasis und sogar Stress und Lärmbelastung profitieren könnten.

In unserer Gruppe befassen wir uns insbesondere mit der Bedeutung von CD11b+ myeloischen Zellen, insbesondere Monozyten/Makrophagen. Wir interessieren uns auch für den Einfluss von Gerinnungsfaktoren des Kontaktphasensystems, der Thrombinverstärkung und des Gewebefaktorsystems bei Gefäßentzündungen.

Forschungsschwerpunkte

• Die Rolle entzündlicher myelomonozytärer Zellen bei Aktivierung des Renin-Angiotension-Aldosteron-Systems

• Das Zusammenspiel von Gerinnungsfaktoren, Leukozyten und Thrombozyten bei vaskulärer Dysfunktion, Ischämischer und Nichtischämischer Herzinsuffizienz und Atherothrombose

• Systemische Rolle der Vaskulären Inflammation im altersabhängigen Niedergang der Organfunktion

Kooperationspartner

• Christian Becker (Dermatologie, Universitätsmedizin Mainz)
• Ari Waisman (Institut für Molekulare Medizin, Universitätsmedizin Mainz)
• Christoph Reinhardt (CTH, Universitätsmedizin Mainz)
• Wolfram Ruf (Alexander von Humboldt-Professur, Universitätsmedizin Mainz)
• Thomas Renné (Karolinska Institutet, Stockholm)
• Zaverio Ruggeri (Scripps Research, La Jolla, USA)
• Miguel Andrade (Institute for Molecular Biology)
• Jens Titze (Duke Singapore, Singapur)
• Philip Tsao (Stanford University School of Medicine, Palo Alto, USA)
• Stefan Tenzer (Paul Klein-Zentrum für Immunintervention, Universitätsmedizin Mainz)

Drittmittelförderung

• Boehringer Ingelheim
• Boehringer Ingelheim Stiftung
• Stiftung für Pathobiochemie und Molekulare Diagnostik
• MAIFOR
• DFG WE 4361/3-1
• DFG WE 4361/4-1
• DFG WE 4361/7-1
• DZHK
• TICARDIO (ITN: H2020-MSCA-ITN-2018; ID 813409)
• BMBF 'Clusters4Future'  (curATime; P8 heartATech)

 

 

Team - Professur Vaskuläre Inflammation

> Homepage Juniorgruppe Karbach

Virchow Fellow

Alumni

• Hendrik Dörschmann
• Anne-Kristin Conze
• Anja Conrad
• Dr. med. Maria Isabel Schmidgen
• Dr. med. Jan Stratmann
• Dr. med. Daniel Minwegen
• Dr. med. vet. Tanja Schönfelder
• Dr. med. Eleni Giokoglu
• Panagiotis Efentakis, PhD
• Jeremy Lagrange, PhD
• Dr. med. Wolf-Stephan Rudi
• Dr. rer. nat. Sabine Kossmann
• Venkat Garlapati, Phd
  

Ausgewählte Originalarbeiten

• Garlapati V, Molitor M, Michna T, Harms GS, Finger S, Jung R, Lagrange J, Efentakis P, Wild J, Knorr M, Karbach S, Wild S, Vujacic-Mirski K, Münzel T, Daiber A, Brandt M, Gori T, Milting H, Tenzer S, Ruf W, Wenzel P. Targeting myeloid cell coagulation signaling blocks MAP kinase/TGF-β1-driven fibrotic remodeling in ischemic heart failure. J Clin Invest. 2023 Feb 15;133(4):e156436
• Brandt M, Dörschmann H, Khraisat S, Knopp T, Ringen J, Kalinovic S, Garlapati V, Siemer S, Molitor M, Göbel S, Stauber R, Karbach SH, Münzel T, Daiber A, Wenzel P. Telomere Shortening in Hypertensive Heart Disease Depends on Oxidative DNA Damage and Predicts Impaired Recovery of Cardiac Function in Heart Failure. Hypertension. 2022 Oct;79(10):2173-2184
• Luo Q, Wenzel P. Properdin (factor P) as a new target cleaved by factor XIa: Intrinsic coagulation at the crossroads with inflammation. Res Pract Thromb Haemost. 2022 Nov 4;6(7):e12835
• Efentakis P, Molitor M, Kossmann S, Bochenek ML, Wild J, Lagrange J, Finger S, Jung R, Karbach S, Schäfer K, Schulz A, Wild P, Münzel T, Wenzel P. Tubulin-folding cofactor E deficiency promotes vascular dysfunction by increased endoplasmic reticulum stress. Eur Heart J. 2022 Feb 10;43(6):488-500
• Molitor M, Rudi WS, Garlapati V, Finger S, Schuler R, Kossmann S, Lagrange J, Nguyen TS, Wild J, Knopp T, Karbach SH, Knorr M, Ruf W, Munzel T, Wenzel P. Nox2+ myeloid cells drive vascular inflammation and endothelial dysfunction in heart failure after myocardial infarction via angiotensin II receptor type 1. Cardiovasc Res. 2021;117:162-177
• Keller K, Hobohm L, Ostad MA, Göbel S, Lankeit M, Konstantinides S, Münzel T, Wenzel P. Temporal trends and predictors of inhospital death in patients hospitalised for heart failure in Germany. Eur J Prev Cardiol. 2021 Aug 9;28(9):990-997
• Rudi WS, Molitor M, Garlapati V, Finger S, Wild J, Münzel T, Karbach SH, Wenzel P. ACE Inhibition Modulates Myeloid Hematopoiesis after Acute Myocardial Infarction and Reduces Cardiac and Vascular Inflammation in Ischemic Heart Failure. Antioxidants (Basel). 2021 Mar 5;10(3):396
• Lagrange J, Finger S, Kossmann S, Garlapati V, Ruf W, Wenzel P. Angiotensin II Infusion Leads to Aortic Dissection in LRP8 Deficient Mice. Int J Mol Sci. 2020;21
• Wenzel P, Kopp S, Göbel S, Jansen T, Geyer M, Hahn F, Kreitner KF, Escher F, Schultheiss HP, Münzel T. Evidence of SARS-CoV-2 mRNA in endomyocardial biopsies of patients with clinically suspected myocarditis tested negative for COVID-19 in nasopharyngeal swab. Cardiovasc Res. 2020 Aug 1;116(10):1661-1663
• Karbach S, Hobohm L, Wild J, Munzel T, Gori T, Wegner J, Steinbrink K, Wenzel P, Keller K. Impact of Psoriasis on Mortality Rate and Outcome in Myocardial Infarction. J Am Heart Assoc. 2020;9:e016956
• Finger S, Knorr M, Molitor M, Schuler R, Garlapati V, Waisman A, Brandt M, Munzel T, Bopp T, Kossmann S, Karbach S, Wenzel P. A sequential interferon gamma directed chemotactic cellular immune response determines survival and cardiac function post-myocardial infarction. Cardiovasc Res. 2019;115:1907-1917
• Jansen T, Kroller-Schon S, Schonfelder T, Foretz M, Viollet B, Daiber A, Oelze M, Brandt M, Steven S, Kvandova M, Kalinovic S, Lagrange J, Keaney JF, Jr., Munzel 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;114:1883-1893
• Subramaniam S, Jurk K, Hobohm L, Jackel S, Saffarzadeh M, Schwierczek K, Wenzel P, Langer F, Reinhardt C, Ruf W. Distinct contributions of complement factors to platelet activation and fibrin formation in venous thrombus development. Blood. 2017;129:2291-2302
• 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. Distinct Regulatory Effects of Myeloid Cell and Endothelial Cell NAPDH Oxidase 2 on Blood Pressure. Circulation. 2017;135:2163-2177
• Kossmann S, Lagrange J, Jackel S, Jurk K, Ehlken M, Schonfelder 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, Renne T, Ruf W, Munzel T, Wenzel P. Platelet-localized FXI promotes a vascular coagulation-inflammatory circuit in arterial hypertension. Sci Transl Med. 2017;9
• Karbach SH, Schonfelder T, Brandao I, Wilms E, Hormann N, Jackel S, Schuler R, Finger S, Knorr M, Lagrange J, Brandt M, Waisman A, Kossmann S, Schafer K, Munzel T, Reinhardt C, Wenzel P. Gut Microbiota Promote Angiotensin II-Induced Arterial Hypertension and Vascular Dysfunction. J Am Heart Assoc. 2016;5
• Wenzel P, Rossmann H, Muller C, Kossmann S, Oelze M, Schulz A, Arnold N, Simsek C, Lagrange J, Klemz R, Schonfelder T, Brandt M, Karbach SH, Knorr M, Finger S, Neukirch C, Hauser F, Beutel ME, Kroller-Schon S, Schulz E, Schnabel RB, Lackner K, Wild PS, Zeller T, Daiber A, Blankenberg S, Munzel 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;36:3437-3446
• Hinkel R, Lange P, Petersen B, Gottlieb E, Ng JK, Finger S, Horstkotte J, Lee S, Thormann M, Knorr M, El-Aouni C, Boekstegers P, Reichart B, Wenzel P, Niemann H, Kupatt C. Heme Oxygenase-1 Gene Therapy Provides Cardioprotection Via Control of Post-Ischemic Inflammation: An Experimental Study in a Pre-Clinical Pig Model. Journal of the American College of Cardiology. 2015;66:154-165
• Kossmann S, Hu H, Steven S, Schonfelder T, Fraccarollo D, Mikhed Y, Brahler M, Knorr M, Brandt M, Karbach SH, Becker C, Oelze M, Bauersachs J, Widder J, Munzel T, Daiber A, Wenzel P. Inflammatory Monocytes Determine Endothelial Nitric-oxide Synthase Uncoupling and Nitro-oxidative Stress Induced by Angiotensin II. The Journal of biological chemistry. 2014;289:27540-27550
• Kossmann S, Schwenk M, Hausding M, Karbach SH, Schmidgen MI, Brandt M, Knorr M, Hu H, Kroller-Schon S, Schonfelder T, Grabbe S, Oelze M, Daiber A, Munzel T, Becker C, Wenzel P. Angiotensin II-Induced Vascular Dysfunction Depends on Interferon-gamma-Driven Immune Cell Recruitment and Mutual Activation of Monocytes and NK-Cells. Arterioscler Thromb Vasc Biol. 2013;33:1313-1319
• Wenzel P, Knorr 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;124:1370-1381
•  Wenzel P, Schuhmacher S, Kienhofer J, Muller J, Hortmann M, Oelze M, Schulz E, Treiber N, Kawamoto T, Scharffetter-Kochanek K, Munzel T, Burkle A, Bachschmid MM, Daiber A. Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction. Cardiovasc Res. 2008;80:280-289.
• Wenzel P, Hink U, Oelze M, Schuppan S, Schaeuble K, Schildknecht S, Ho KK, Weiner H, Bachschmid M, Munzel T, Daiber A. Role of reduced lipoic acid in the redox regulation of mitochondrial aldehyde dehydrogenase (ALDH-2) activity. Implications for mitochondrial oxidative stress and nitrate tolerance. J Biol Chem. 2007;282:792-799

Ausgewählte Reviews

• Wild J, Wenzel P. Myeloid cells, tissue homeostasis, and anatomical barriers as innate immune effectors in arterial hypertension. J Mol Med (Berl). 2021 Mar;99(3):315-326
• Jung R, Wild J, Ringen J, Karbach S, Wenzel P. Innate Immune Mechanisms of Arterial Hypertension and Autoimmune Disease. Am J Hypertens. 2021 Mar 11;34(2):143-153
• Wenzel P. Monocytes as immune targets in arterial hypertension. Br J Pharmacol. 2019;176:1966-1977
• Lagrange J, Wenzel P. The regulatory role of coagulation factors in vascular function. Frontiers in bioscience. 2019;24:494-513
• Karbach S, Lagrange J, Wenzel P. Thromboinflammation and Vascular Dysfunction. Hamostaseologie. 2019;39:180-187
• Wenzel P. Monocytes as immune targets in arterial hypertension. Br J Pharmacol. 2019 Jun;176(12):1966-1977
• Wenzel P, Kossmann S, Munzel T, Daiber A. Redox regulation of cardiovascular inflammation - Immunomodulatory function of mitochondrial and Nox-derived reactive oxygen and nitrogen species. Free Radic Biol Med. 2017;109:48-60

Editorials, Kommentare und sonstige Fachbeiträge

• Wenzel P. Thromboinflammation in cardiovascular disease: lessons learned for the management of hypertension, heart failure, and aortic valve stenosis. Eur Heart J. 2022 Nov 21;43(44):4611-4613
• Schäfer K, Wenzel P. When big eaters stop feasting: loss of metabolic control in macrophages exacerbates hypertension in obesity. Cardiovasc Res. 2021 Jan 21;117(2):351-353
• Knopp T, Karbach S, Wenzel P. Myeloid Cells to the Rescue: Improving Thrombus Resolution. Thromb Haemost. 2020 Feb;120(2):197-198
• Carnevale D, Wenzel P. Mechanical stretch on endothelial cells interconnects innate and adaptive immune response in hypertension. Cardiovasc Res. 2018 Sep 1;114(11):1432-1434
• Brandt M, Wenzel P. Alcohol puts the heart under pressure: Acetaldehyde activates a localized renin angiotensin aldosterone system within the myocardium in alcoholic cardiomyopathy. Int J Cardiol. 2018 Apr 15;257:220-221
• Kossmann S, Wenzel P. Under Pressure: A New Role for CD11c⁺ Myeloid Cells in Hypertension. Hypertension. 2018 Apr;71(4):557-558
• Wenzel P. Organic Nitrates in Heart Failure Revisited: Pentaerythritol Tetranitrate Induces Heme Oxygenase 1 to Protect the Myocardium. Hypertension. 2015 Nov;66(5):933-4