Immune checkpoint signalling in acute myocardial infarction
Team
Dr. med.
Lars Michel
Leitungsteam
Armin Spomer
MD candidate
Topics and Vision
Myocardial inflammation plays a key role in the development and healing of acute myocardial infarction (AMI). A better understanding of the specific mechanisms forms the basis for the identification of new target structures for the development of innovative therapeutic approaches.
The research group focuses on the regulation of the adaptive immune response after AMI with a focus on the immune checkpoint Programmed cell death protein 1 (PD1), which has a crucial but so far incompletely understood cardioprotective function.
A translational concept with the application of innovative methodology and direct clinical linkage ensures a holistic research approach with high clinical relevance. Extensive preliminary work on myocardial immune regulation through immune checkpoints in the field of cardio-oncology and close networking at the site provide a technical and content transfer.
Projects
The relevance of cardiac Programmed cell death protein 1 signalling at baseline and acute myocardial infarction
Clinical and basic science data suggest that the Programmed cell death protein 1 (PD1) immune checkpoint plays an essential role in maintaining the immunological integrity of the heart. This project provides a comprehensive basic science characterisation of the relevance of PD1 and the ligand PDL1 under basal conditions and in acute myocardial infarction.
Targeting cardiac endothelial Programmed cell death protein 1 ligand 1 (PDL1) in acute myocardial infarction
PDL1 is densely expressed on cardiac endothelial cells and regulates cardiac immune homeostasis by ligating PD1 on lymphocytes. This project aims to characterize how PDL1 prevents deleterious inflammation following acute myocardial infarction. By increasing cardiac PDL1 expression using an experimental epigenetic approach, we aim to test a novel strategy for cardioprotection.
Soluble Programmed cell death protein 1 ligand 1 (sPDL1) as a biomarker in acute myocardial infarction
sPDL1 is an experimental biomarker to assess PD1/PDL1 activity and has already been successfully used to test the response to cancer therapy in different settings. Here, we aim to assess as sPDL1 to predict the outcome of acute myocardial infarction as a biomarker in vitro and in a translational approach in patients‘ samples.
Methods
• Models
• In-vivo ischaemia/reperfusion model
• Pdcd1-/- model
• Cardiac endothelial cell culture
• In vitro hypoxia/reoxygenation
• Imaging
• Light microscopy
• Confocal microscopy
• Electron microscopy
• Lightsheet fluorescence microscope
• Hemodynamics
• Echocardiography
• Pressure/volume catheterization
• Molecular
• Western blot
• PCR, Real-time PCR
• Cytokine array
• Various ELISAs
• Flow cytometry
• Translational
• Acute myocardial infarction patients‘s samples (pending)
• Clinical data
Funding
• IFORES research grant of the Medical Faculty, University Duisburg-Essen
Five relevant publications
Michel L, Helfrich I, Hendgen-Cotta UB, Mincu RI, Korste S, Mrotzek SM, Spomer A, Odersky A, Rischpler C, Herrmann K, Umutlu L, Coman C, Ahrends R, Sickmann A, Löffek S, Livingstone E, Ugurel S, Zimmer L, Gunzer M, Schadendorf D, Totzeck M, Rassaf T. Targeting early stages of cardiotoxicity from anti-PD1 immune checkpoint inhibitor therapy. Eur Heart J. 2022 Jan 31;43(4):316-329. doi: 10.1093/eurheartj/ehab430. PMID: 34389849.
Michel L, Korste S, Spomer A, Hendgen-Cotta UB, Rassaf T, Totzeck M. PD1 Deficiency Modifies Cardiac Immunity during Baseline Conditions and in Reperfused Acute Myocardial Infarction. Int J Mol Sci. 2022 Jul 7;23(14):7533. doi: 10.3390/ijms23147533. PMID: 35886878; PMCID: PMC9321105.
Korste S, Settelmeier S, Michel L, Odersky A, Stock P, Reyes F, Haj-Yehia E, Anker MS, Grüneboom A, Hendgen-Cotta UB, Rassaf T, Totzeck M. Anthracycline Therapy Modifies Immune Checkpoint Signaling in the Heart. Int J Mol Sci. 2023 Mar 23;24(7):6052. doi: 10.3390/ijms24076052. PMID: 37047026; PMCID: PMC10094326.
Michel L, Stock P, Rammos C, Totzeck M, Rassaf T, Hendgen-Cotta UB. Real-time Pressure-volume Analysis of Acute Myocardial Infarction in Mice. J Vis Exp 2018 Jul 2;(137):57621.
Michel L, Totzeck M, Lehmann L, Finke D. Emerging role of immune checkpoint inhibitors and their relevance for the cardiovascular system. Herz. 2020 Nov;45(7):645-651.
Awards
11/2022 Promotional award of the Hans und Gertie Fischer Foundation
04/2022 Presentation as „Best of Congress”, German Society of Cardiology
11/2020 Day of Science poster price of the Medical Faculty, University Duisburg-Essen (Armin Spomer)
12/2019 Best Paper Award, Medical Faculty, University of Duisburg-Essen
08/2019 ESC Congress Educational Grant, European Society of Cardiology
04/2019 Poster Award, German Society of Cardiology
07/2018 ESC Basic Science Travel Grant, European Society of Cardiology
10/2013 Young Investigators‘ Award, German Society of Cardiology