Fraunhofer Institute for Toxicology and Experimental MedicineThe heart and lungs interact in a complex interplay. Both systems are affected by partly similar risk factors and there is an overlap of pathogenic molecular mechanisms such as organ fibrosis. Due to high morbidity and mortality, diseases of the heart and lungs play a major role in terms of health economics.
Cardiopulmonary research
Research for healthy hearts and lungs
A synergetic development
Establishment of a university-affiliated Division of Cardiovascular Research in 2021 has generated new methodological and scientific overlaps at Fraunhofer ITEM. As a result, the long-standing expertise in lung research is experiencing a synergetic further development of high clinical relevance. RNA molecules in particular are being investigated very successfully as diagnostic biomarkers and therapeutic targets for the benefit of patients with cardiac and pulmonary diseases. Computer-assisted translational bioinformatics, used to predict molecular mechanisms based on RNA molecules, is of particular importance in this context. Fraunhofer ITEM researchers are currently exploring the potential of RNAs for toxicology and efficacy testing of drugs.
Advancing ideas to the proof of concept
Through their clinical research, Fraunhofer ITEM scientists enable a direct transfer of findings to humans, for example, by using chip cytometry and exhaled breath analysis.
To efficiently translate ideas from bench to bedside, the scientists use appropriate exposure systems, some of which have been developed specifically for this purpose, and innovative model systems that closely mimic the situation in patients. They use the generated data to further develop and refine their modeling approaches, so as to allow in-vitro results or findings to be extrapolated both qualitatively and quantitatively for the prediction of the expected in-vivo effect in humans. Candidate drugs can be tested at the institute for their efficacy and side effects to provide the proof of concept in humans, i.e. the necessary evidence of the drug’s mode of action.
Publications
- Arbustini, E., Behr, E. R., Carrier, L., van Duijn, C., Evans, P., Favalli, V., van der Harst, P., Haugaa, K. H., Jondeau, G., Kaab, S., Kaski, J. P., Kavousi, M., Loeys, B., Pantazis, A., Pinto, Y., Schunkert, H., Di Toro, A., Thum, T., Urtis, M., Waltenberger, J., Elliott, P. (2022). Interpretation and actionability of genetic variants in cardiomyopathies: a position statement from the European Society of Cardiology Council on cardiovascular genomics. European Heart Journal [Epub ahead of print]: 17 p. doi: 10.1093/eurheartj/ehab895 https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehab895/6516788 - Open Access
- Badi, Y. E., Pavel, A. B., Pavlidis, S., Riley, J. H., Bates, S., Kermani, N. Z., Knowles, R., Kolmert, J., Wheelock, C. E., Worsley, S., Uddin, M., Alving, K., Bakke, P. S., Behndig, A., Caruso, M., Chanez, P., Fleming, L. J., Fowler, S. J., Frey, U., Howarth, P., Horvath, I., Krug, N., Maitland-van der Zee, A. H., Montuschi, P., Roberts, G., Sanak, M., Shaw, D. E., Singer, F., Sterk, P. J., Djukanovic, R., Dahlen, S. E., Guo, Y. K., Chung, K. F., Guttman-Yassky, E., Adcock, I. M., Group, U. B. S. (2022). Mapping atopic dermatitis and anti-IL-22 response signatures to type 2-low severe neutrophilic asthma. Journal of Allergy and Clinical Immunology 149(1): 89-101. doi: 10.1016/j.jaci.2021.04.010 https://www.sciencedirect.com/science/article/abs/pii/S0091674921006485?via%3Dihub
- Bei, Y., Lu, D., Bar, C., Chatterjee, S., Costa, A., Riedel, I., Mooren, F. C., Zhu, Y., Huang, Z., Wei, M., Hu, M., Liu, S., Yu, P., Wang, K., Thum, T., Xiao, J. (2022). miR-486 attenuates cardiac ischemia/reperfusion injury and mediates the beneficial effect of exercise for myocardial protection. Molecular Therapy 30(4): 1675-1691. doi: 10.1016/j.ymthe.2022.01.031 https://www.sciencedirect.com/science/article/abs/pii/S1525001622000314?via%3Dihub -
- Biener, M., Giannitsis, E., Thum, T., Bar, C., Stoyanov, K. M., Salbach, C., de Gonzalo-Calvo, D., Frey, N., Mueller-Hennessen, M. (2022). Prognostic value of circulating microRNAs compared to high-sensitivity troponin T in patients presenting with suspected acute coronary syndrome to the emergency department. Clinical Biochemistry 99: 9-16. doi: 10.1016/j.clinbiochem.2021.09.009 https://www.sciencedirect.com/science/article/abs/pii/S0009912021002502?via%3Dihub
- Carstensen, S., Benediktus, E., Litzenburger, T., Hohlfeld, J. M., Muller, M. (2022). Basophil activation test: Assay precision and BI 1002494 SYK inhibition in healthy and mild asthmatics. Cytometry A 101(1): 86-94. doi: 10.1002/cyto.a.24338 https://onlinelibrary.wiley.com/doi/10.1002/cyto.a.24338 - Open Access
- Costa, A., Cushman, S., Haubner, B. J., Derda, A. A., Thum, T., Bar, C. (2022). Neonatal injury models: integral tools to decipher the molecular basis of cardiac regeneration. Basic Research in Cardiology 117(1): 26. doi: 10.1007/s00395-022-00931-w https://link.springer.com/article/10.1007/s00395-022-00931-w - Open Access
- Davidson, S. M., Boulanger, C. M., Aikawa, E., Badimon, L., Barile, L., Binder, C. J., Brisson, A., Buzas, E., Emanueli, C., Jansen, F., Katsur, M., Lacroix, R., Lim, S. K., Mackman, N., Mayr, M., Menasche, P., Nieuwland, R., Sahoo, S., Takov, K., Thum, T., Vader, P., Wauben, M. H. M., Witwer, K., Sluijter, J. P. G. (2022). Methods for the identification and characterization of extracellular vesicles in cardiovascular studies - from exosomes to microvesicles. Cardiovascular Research [Epub ahead of print]. doi: 10.1093/cvr/cvac031 https://academic.oup.com/cardiovascres/advance-article-abstract/doi/10.1093/cvr/cvac031/6553781?redirectedFrom=fulltext
- de Boer, R. A., Heymans, S., Backs, J., Carrier, L., Coats, A. J. S., Dimmeler, S., Eschenhagen, T., Filippatos, G., Gepstein, L., Hulot, J. S., Knoll, R., Kupatt, C., Linke, W. A., Seidman, C. E., Tocchetti, C. G., van der Velden, J., Walsh, R., Seferovic, P. M., Thum, T. (2022). Targeted therapies in genetic dilated and hypertrophic cardiomyopathies: from molecular mechanisms to therapeutic targets. A position paper from the Heart Failure Association (HFA) and the Working Group on Myocardial Function of the European Society of Cardiology (ESC). European Journal of Heart Failure 24(3): 406-420. doi: 10.1002/ejhf.2414 https://onlinelibrary.wiley.com/doi/10.1002/ejhf.2414 - Open Access
- De Sadeleer, L. J., Verleden, S. E., Schupp, J. C., McDonough, J. E., Goos, T., Yserbyt, J., Bargagli, E., Rottoli, P., Kaminski, N., Prasse, A., Wuyts, W. A. (2022). BAL Transcriptomes Characterize Idiopathic Pulmonary Fibrosis Endotypes With Prognostic Impact. Chest [Epub ahead of print]. doi: 10.1016/j.chest.2021.12.668 https://www.sciencedirect.com/science/article/abs/pii/S0012369222000538?via%3Dihub
- Gonzalez, A., Richards, A. M., de Boer, R. A., Thum, T., Arfsten, H., Hulsmann, M., Falcao-Pires, I., Diez, J., Foo, R. S. Y., Chan, M. Y., Aimo, A., Anene-Nzelu, C. G., Abdelhamid, M., Adamopoulos, S., Anker, S. D., Belenkov, Y., Gal, T. B., Cohen-Solal, A., Bohm, M., Chioncel, O., Delgado, V., Emdin, M., Jankowska, E. A., Gustafsson, F., Hill, L., Jaarsma, T., Januzzi, J. L., Jhund, P. S., Lopatin, Y., Lund, L. H., Metra, M., Milicic, D., Moura, B., Mueller, C., Mullens, W., Nunez, J., Piepoli, M. F., Rakisheva, A., Ristic, A. D., Rossignol, P., Savarese, G., Tocchetti, C. G., Van Linthout, S., Volterrani, M., Seferovic, P., Rosano, G., Coats, A. J. S., Bayes-Genis, A. (2022). Cardiac remodelling - Part 1: From cells and tissues to circulating biomarkers. A review from the Study Group on Biomarkers of the Heart Failure Association of the European Society of Cardiology. European Journal of Heart Failure [Epub ahead of print]. doi: 10.1002/ejhf.2493 https://onlinelibrary.wiley.com/doi/10.1002/ejhf.2493 - Open Access
- Heratizadeh, A., Roesner, L. M., Traidl, S., Moitinho-Silva, L., Ellinghusen, B., Rodriguez, E., Harder, I., Sapak, M., Weidinger, S., Badorrek, P., Hohlfeld, J. M., Werfel, T. (2022). Basic skin therapy effects on skin inflammation and microbiome composition in patients with atopic dermatitis after challenges with grass pollen. Journal of the European Academy of Dermatology and Venereology [Epub ahead of print]. doi: 10.1111/jdv.17966 https://onlinelibrary.wiley.com/doi/10.1111/jdv.17966
- Herrera, V. L. M., Walkey, A. J., Nguyen, M. Q., Gromisch, C. M., Mosaddhegi, J. Z., Gromisch, M. S., Jundi, B., Lukassen, S., Carstensen, S., Denis, R., Belkina, A. C., Baron, R. M., Pinilla-Vera, M., Mueller, M., Kimberly, W. T., Goldstein, J. N., Lehmann, I., Shih, A. R., Eils, R., Levy, B. D., Ruiz-Opazo, N. (2022). A targetable 'rogue' neutrophil-subset, [CD11b+DEspR+] immunotype, is associated with severity and mortality in acute respiratory distress syndrome (ARDS) and COVID-19-ARDS. Scientific Reports 12(1): 5583. doi: 10.1038/s41598-022-09343-1 https://www.nature.com/articles/s41598-022-09343-1 - Open Access
- Hoda, U., Pavlidis, S., Bansal, A. T., Takahashi, K., Hu, S., Ng Kee Kwong, F., Rossios, C., Sun, K., Bhavsar, P., Loza, M., Baribaud, F., Chanez, P., Fowler, S. J., Horvath, I., Montuschi, P., Singer, F., Musial, J., Dahlen, B., Krug, N., Sandstrom, T., Shaw, D. E., Lutter, R., Fleming, L. J., Howarth, P. H., Caruso, M., Sousa, A. R., Corfield, J., Auffray, C., De Meulder, B., Lefaudeux, D., Dahlen, S. E., Djukanovic, R., Sterk, P. J., Guo, Y., Adcock, I. M., Chung, K. F., group, U. B. s. (2022). Clinical and transcriptomic features of persistent exacerbation-prone severe asthma in U-BIOPRED cohort. Clin Transl Med 12(4): e816. doi: 10.1002/ctm2.816 https://onlinelibrary.wiley.com/doi/10.1002/ctm2.816 - Open Access
- Holz, O., Muller, M., Carstensen, S., Olin, A. C., Hohlfeld, J. M. (2022). Inflammatory cytokines can be monitored in exhaled breath particles following segmental and inhalation endotoxin challenge in healthy volunteers. Scientific Reports 12(1): 5620. doi: 10.1038/s41598-022-09399-z https://www.nature.com/articles/s41598-022-09399-z - Open Access
- Holz, O., van Vorstenbosch, R., Guenther, F., Schuchardt, S., Trinkmann, F., van Schooten, F. J., Smolinska, A., Hohlfeld, J. M. (2022). Changes of breath volatile organic compounds in healthy volunteers following segmental and inhalation endotoxin challenge. Journal of Breath Research 16(3). doi: 10.1088/1752-7163/ac6359 https://iopscience.iop.org/article/10.1088/1752-7163/ac6359 - Open Access
- Kreutzer, F. P., Meinecke, A., Mitzka, S., Hunkler, H. J., Hobuss, L., Abbas, N., Geffers, R., Weusthoff, J., Xiao, K., Jonigk, D. D., Fiedler, J., Thum, T. (2022). Development and characterization of anti-fibrotic natural compound similars with improved effectivity. Basic Research in Cardiology 117(1): 9. doi: 10.1007/s00395-022-00919-6 https://link.springer.com/article/10.1007/s00395-022-00919-6 - Open Access
- Kreutzer, F. P., Meinecke, A., Schmidt, K., Fiedler, J., Thum, T. (2022). Alternative strategies in cardiac preclinical research and new clinical trial formats. Cardiovascular Research 118(3): 746-762. doi: 10.1093/cvr/cvab075 https://academic.oup.com/cardiovascres/article/118/3/746/6162160 - Open Access
- Leonardy, J., Bar, C. (2022). Editorial Research Topic: Non-coding RNA as Therapeutic Target: A Game Changer in Cardiac Regenerative Strategies? Frontiers in Physiology 12: 822280. doi: 10.3389/fphys.2021.822280 https://www.frontiersin.org/articles/10.3389/fphys.2021.822280/full - Open Access
- Lu, D., Chatterjee, S., Xiao, K., Riedel, S., Huang, C., Costa, A., Cushman, S., Neufeldt, D., Rode, L., Schmidt, A., Juchem, M., Leonardy, J., Büchler, G., Blume, J., Gern, O., Kalinke, U., Tan, W., Foo, R., Vink, A., van Laake L., van der Meer, P., Bär, C., Thum, T. (2022). A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity. European Heart Journal. doi: 10.1093/ehac337 https://doi.org/10.1093/eurheartj/ehac337
- Makarewich, C. A., Thum, T. (2022). Exercise-Induced Long Noncoding RNAs As New Players in Cardiac Hypertrophy. Circulation 145(16): 1234-1237. doi: 10.1161/CIRCULATIONAHA.122.059278 https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.122.059278
- Mullens, W., Martens, P., Testani, J. M., Tang, W. H. W., Skouri, H., Verbrugge, F. H., Fudim, M., Iacoviello, M., Franke, J., Flammer, A. J., Palazzuoli, A., Barragan, P. M., Thum, T., Marcos, M. C., Miro, O., Rossignol, P., Metra, M., Lassus, J., Orso, F., Jankowska, E. A., Chioncel, O., Milicic, D., Hill, L., Seferovic, P., Rosano, G., Coats, A., Damman, K. (2022). Renal effects of guideline directed medical therapies in heart failure - a consensus document from the Heart Failure Association of the European Society of Cardiology. European Journal of Heart Failure [Epub ahead of print]. doi: 10.1002/ejhf.2471 https://onlinelibrary.wiley.com/doi/10.1002/ejhf.2471 - Open Access
- Obernolte, H., Niehof, M., Braubach, P., Fieguth, H. G., Jonigk, D., Pfennig, O., Tschernig, T., Warnecke, G., Braun, A., Sewald, K. (2022). Cigarette smoke alters inflammatory genes and the extracellular matrix - investigations on viable sections of peripheral human lungs. Cell and Tissue Research 387(2): 249-260. doi: 10.1007/s00441-021-03553-1 https://link.springer.com/article/10.1007/s00441-021-03553-1 - Open Access
- Obert, A. J., Gutberlet, M., Kern, A. L., Kaireit, T. F., Glandorf, J., Moher Alsady, T., Wacker, F., Hohlfeld, J. M., Vogel-Claussen, J. (2022). Examining lung microstructure using (19) F MR diffusion imaging in COPD patients. Magnetic Resonance in Medicine [Epub ahead of print]. doi: 10.1002/mrm.29237 https://onlinelibrary.wiley.com/doi/10.1002/mrm.29237 - Open Access
- Preuss, E. B., Schubert, S., Werlein, C., Stark, H., Braubach, P., Hofer, A., Plucinski, E. K. J., Shah, H. R., Geffers, R., Sewald, K., Braun, A., Jonigk, D. D., Kuhnel, M. P. (2022). The challenge of long-term cultivation of human precision-cut lung slices. American Journal of Pathology 192(2): 239-253. doi: 10.1016/j.ajpath.2021.10.020 https://www.sciencedirect.com/science/article/pii/S0002944021004818?via%3Dihub - Open Access
- Sparreman Mikus, M., Kolmert, J., Andersson, L. I., Ostling, J., Knowles, R. G., Gomez, C., Ericsson, M., Thorngren, J. O., Emami Khoonsari, P., Dahlen, B., Kupczyk, M., De Meulder, B., Auffray, C., Bakke, P. S., Beghe, B., Bel, E. H., Caruso, M., Chanez, P., Chawes, B., Fowler, S. J., Gaga, M., Geiser, T., Gjomarkaj, M., Horvath, I., Howarth, P. H., Johnston, S. L., Joos, G., Krug, N., Montuschi, P., Musial, J., Nizankowska-Mogilnicka, E., Olsson, H. K., Papi, A., Rabe, K. F., Sandstrom, T., Shaw, D. E., Siafakas, N. M., Uhlen, M., Riley, J. H., Bates, S., Middelveld, R. J. M., Wheelock, C. E., Chung, K. F., Adcock, I. M., Sterk, P. J., Djukanovic, R., Nilsson, P., Dahlen, S. E., James, A., Group, U. B. S., the, B. C. (2022). Plasma proteins elevated in severe asthma despite oral steroid use and unrelated to Type-2 inflammation. European Respiratory Journal 59(2). doi: 10.1183/13993003.00142-2021 https://erj.ersjournals.com/content/59/2/2100142.long -
- Thum, T. (2022). Orchestration of vascular smooth muscle cell plasticity using epigenetic therapy. European Heart Journal [Epub ahead of print]. doi: 10.1093/eurheartj/ehac200 https://academic.oup.com/eurheartj/advance-article/doi/10.1093/eurheartj/ehac200/6572530 - Open Access
- van der Velden, J., Asselbergs, F. W., Bakkers, J., Batkai, S., Bertrand, L., Bezzina, C. R., Bot, I., Brundel, B., Carrier, L., Chamuleau, S., Ciccarelli, M., Dawson, D., Davidson, S. M., Dendorfer, A., Duncker, D. J., Eschenhagen, T., Fabritz, L., Falcao-Pires, I., Ferdinandy, P., Giacca, M., Girao, H., Gollmann-Tepekoylu, C., Gyongyosi, M., Guzik, T. J., Hamdani, N., Heymans, S., Hilfiker, A., Hilfiker-Kleiner, D., Hoekstra, A. G., Hulot, J. S., Kuster, D. W. D., van Laake, L. W., Lecour, S., Leiner, T., Linke, W. A., Lumens, J., Lutgens, E., Madonna, R., Maegdefessel, L., Mayr, M., van der Meer, P., Passier, R., Perbellini, F., Perrino, C., Pesce, M., Priori, S., Remme, C. A., Rosenhahn, B., Schotten, U., Schulz, R., Sipido, K., Sluijter, J. P. G., van Steenbeek, F., Steffens, S., Terracciano, C. M., Tocchetti, C. G., Vlasman, P., Yeung, K. K., Zacchigna, S., Zwaagman, D., Thum, T. (2022). Animal models and animal-free innovations for cardiovascular research: current status and routes to be explored. Consensus document of the ESC working group on myocardial function and the ESC Working Group on Cellular Biology of the Heart. Cardiovascular Research [Epub ahead of print]. doi: 10.1093/cvr/cvab370 https://academic.oup.com/cardiovascres/advance-article/doi/10.1093/cvr/cvab370/6499268 -
- Voskrebenzev, A., Kaireit, T. F., Klimeš, F., Pöhler, G. H., Behrendt, L., Biller, H., Berschneider, K., Wacker, F., Welte, T., Hohlfeld, J. M., Vogel-Claussen, J. (2022). PREFUL MRI Depicts Dual Bronchodilator Changes in COPD: A Retrospective Analysis of a Randomized Controlled Trial. Radiology: Cardiothoracic Imaging 4(2). doi: 10.1148/ryct.210147 https://pubs.rsna.org/doi/full/10.1148/ryct.210147 - Open Access