Cardiovascular disorders, including cardiac insufficiency (commonly known as heart failure), coronary heart disease and heart attacks are some of the most common causes of death worldwide. For this reason, further research into timely prevention and diagnosis as well as the development of new treatment strategies are particularly important for these disorders. As part of the »Molecular Mechanisms of Cardiac Insufficiency« project, ISAS researchers are working to decode the disease mechanisms of cardiac insufficiency and identify key structures relevant to treatment at molecular level. The objective of this work is to identify new diagnostic and therapeutic target molecules for various cardiac diseases such as heart failure. Furthermore, the researchers are working to explain the cardiotoxic mechanisms of cancer medications, for example.
Combination of methods for early diagnosis and improved treatment
To achieve a differentiated investigation not only into individual components but also entire cellular systems, it is necessary to apply a combination of various analysis methods. That is why the researchers are combining, among other things, traditional molecular genetic and biochemical methods with high throughput methods. They are also investigating the potential offered by cold atmospheric plasmas (CAP) in the treatment of cardiac insufficiency.
In order to achieve an improved and early diagnosis of the disease using identified specific biomarkers, spectroscopic imaging methods are additionally being employed in this research project. Such methods provide clarification of the role played by the heart not only in the case of cardiac insufficiency but also in the case of metabolic disorders and storage diseases such as Fabry disease. For example, the researchers succeeded for the first time in identifying subtle changes in the protein-lipid content between heart tissue affected by Fabry disease and healthy tissue by using coherent anti-Stokes Raman scattering (CARS) microscopy in a murine model. This diagnostic method has the potential to underpin other means of diagnosis in order to determine the involvement of certain organs.
Share
Select publications
Pharmacological Research, Vol. 211, 2024, P. 107558
Brand T, Baumgarten BT, Denzinger S, Reinders Y, Kleindl M, Schanbacher C, Funk F, Gedik N, Jabbasseh M, Kleinbongard P, Dudek J, Szendroedi J,…
From Ca2+ dysregulation to heart failure: β-adrenoceptor activation by RKIP postpones molecular damages and subsequent cardiac dysfunction in mice carrying mutant PLNR9C by correction of aberrant Ca2+-handling
https://doi.org/10.1016/j.phrs.2024.107558
Redox Biology, Vol. 2024, No. 77, 2024
Raabe J, Wittig I, Laurette P, Stathopoulou K, Brand T, Schulze T, Klampe B, Orthey E, Cabrera-Orefice A, Meisterknecht J, Thiemann E, Laufer SD,…
Physioxia rewires mitochondrial complex composition to protect stem cell viability
https://doi.org/10.1016/j.redox.2024.103352
Cardiovascular Research, Vol. 120, No. 15, 2024
Reyat JSS, Sommerfeld LC, O’Reilly M, Cardoso VR, Thiemann E, Khan A, O’Shea C, Harder S, Müller C, Barlow J, Stapley RJ, Chua W, Kabir SN,…
PITX2 deficiency leads to atrial mitochondrial dysfunction
https://doi.org/10.1093/cvr/cvae169
MMW Fortschritte der Medizin, Vol. 166, No. 13, 2024, P. 44-47
Lorenz K, Knaup J.
Nach Krankenhausaufenthalt: Wie die Behandlung weiterführen? Multimorbider Patient mit eingeschränkter Nierenfunktion
https://doi.org/10.1007/s15006-024-4117-7
Naunyn-Schmiedeberg's Archives of Pharmacology, 2024
Fender J, Klöcker J, Boivin-Jahns V, Ravens U, Jahns R, Lorenz K.
“Cardiac glycosides”—quo vaditis?—past, present, and future?
https://doi.org/10.1007/s00210-024-03285-3
Current Opinion in Pharmacology, Vol. 2024, No. 76, 2024
Brand T, Lukannek A, Boivin-Jahns V, Jahns R, Lorenz K.
From “contraindicated” to “first line” – Current mechanistic insights beyond canonical β-receptor signaling
https://doi.org/10.1016/j.coph.2024.102458
Thyroid, 2024, P. 1-27
Geist D, Hönes S, Grund S, Pape J, Siemes D, Spangenberg P, Tolstik E, Dörr S, Spielmann N, Fuchs H, Gailus-Durner V, Hrabě de Angelis M, Mittag J,…
Canonical and noncanonical contribution of thyroid hormone receptor isoforms alpha and beta to cardiac hypertrophy and heart rate in male mice
https://doi.org/10.1089/thy.2023.0683
Frontiers in Endocrinology, Vol. 15, No. 1339741, 2024, P. 1339741
Kerp H, Gassen J, Grund S, Hönes GS, Dörr S, Mittag J, Härting N, Kaiser FJ, Lorenz K, Führer D.
Cardiac recovery from pressure overload is not altered by thyroid hormone status in old mice
https://doi.org/10.3389/fendo.2024.1339741
Trends in Biotechnology, Vol. 42, No. 2, 2023, P. 212-227
Tolstik E, Lehnart SE, Soeller C, Lorenz K, Sacconi L.
Cardiac multiscale bioimaging: from nano- through micro- to mesoscales.
https://doi.org/10.1016/j.tibtech.2023.08.007
Molecular Metabolism, Vol. 79, 2023, P. 101859
Janz A, Walz K, Cirnu A, Surjanto J, Urlaub D, Leskien M, Kohlhaas M, Nickel A, Brand T, Nose N, Wörsdörfer P, Wagner N, Higuchi T, Maack C, Dudek J,…
Mutations in DNAJC19 cause altered mitochondrial structure and increased mitochondrial respiration in human iPSC-derived cardiomyocytes
https://doi.org/10.1016/j.molmet.2023.101859
Chemistry-A European Journal, Vol. 30, No. 11, 2023, P. e202303506
Sink A, Gerwe H, Hübner H, Boivin-Jahns V, Fender J, Lorenz K, Gmeiner P, Decker M.
"Photo-Adrenalines": ß2-Adrenergic Receptor Agonists as Molecular Probes for the Study of Spatiotemporal Adrenergic Signaling
https://doi.org/10.1002/chem.202303506
Physiological Reports, Vol. 11, No. 17, 2023
Künzel SR, Winter L, Hoffmann M, Kant TA, Thiel J, Kronstein-Wiedemann R, Klapproth E, Lorenz K, El-Armouche A, Kämmerer S.
Investigation of mesalazine as an antifibrotic drug following myocardial infarction in male mice
https://doi.org/10.14814/phy2.15809
Cells, Vol. 12, No. 13, 2023, P. 1780
Bazgir F, Nau J, Nakhaei-Rad S, Amin E, Wolf MJ, Saucerman JJ, Lorenz K, Ahmadian MR.
The Microenvironment of the Pathogenesis of Cardiac Hypertrophy
http://doi.org/10.3390/cells12131780
Nature Communications, Vol. 14, No. 1, 2023
Dore R, Watson L, Hollidge S, Krause C, Sentis SC, Oelkrug R, Geißler C, Johann K, Pedaran M, Lyons G, Lopez-Alcantara N, Resch J, Sayk F, Iwen A,…
Resistance to thyroid hormone induced tachycardia in RTHα syndrome
https://doi.org/10.1038/s41467-023-38960-1
Angewandte Chemie - International Edition, Vol. 62, No. 49, 2023, P. e202306176
Steinmüller SAM, Fender J, Deventer MH, Tutov A, Lorenz K, Stove CP, Hislop JN, Decker M.
Visible-Light Photoswitchable Benzimidazole Azo-Arenes as β-Arrestin2-Biased Selective Cannabinoid 2 Receptor Agonists
https://doi.org/10.1002/anie.202306176
GIT Labor-Fachzeitschrift, Vol. 2023, No. 4, 2023, P. 37
Tolstik E, Lorenz K.
Biospektroskopie für Herzgewebecharakterisierung: Raman-Spektroskopie in der kardiovaskulären Forschung und Diagnostik
https://analyticalscience.wiley.com/content/article-do/biospektroskopie-f%C3%BCr-herzgewebecharakterisierung
Circulation Research, Vol. 132, No. 4, 2023, P. 400-414
Cachorro E, Günscht M, Schubert M, Sadek MS, Siegert J, Dutt F, Bauermeister C, Quickert S, Berning H, Nowakowski F, Lämmle S, Firneburg R, Luo X,…
CNP Promotes Antiarrhythmic Effects via Phosphodiesterase 2
https://doi.org/10.1161/CIRCRESAHA.122.322031
Biomedicines, Vol. 11, No. 2, 2023, P. 559
Schanbacher C, Hermanns HM, Lorenz K, Wajant H, Lang I.
Complement 1q/Tumor Necrosis Factor‐Related Proteins (CTRPs): Structure, Receptors and Signaling
https://doi.org/10.3390/biomedicines11020559
Journal of Molecular and Cellular Cardiology, Vol. 2022, No. 173, 2022, P. S150-S150
Schanbacher C, Bieber M, Reinders Y, Teichert C, Sickmann A, Kleinschnitz C, Langhauser F, Lorenz K.
The extracellular signal-regulated kinases ERK1/2 are detrimental in ischemic stroke
https://doi.org/10.1016/j.yjmcc.2022.08.294
Nature Communications, Vol. 13, No. 1, 2022, P. 7648
Klapproth E, Witt A, Klose P, Wiedemann J, Vavilthota N, Künzel SR, Kämmerer S, Günscht M, Sprott D, Lesche M, Rost F, Dahl A, Rauch E, Kattner L,…
Targeting cardiomyocyte ADAM10 ectodomain shedding promotes survival early after myocardial infarction
https://doi.org/10.1038/s41467-022-35331-0
ACS Chemical Neuroscience, Vol. 13, No. 16, 2022, P. 2410-2435
Rodríguez-Soacha DA, Steinmüller SAM, Işbilir A, Fender J, Deventer MH, Ramírez YA, Tutov A, Sotriffer C, Stove CP, Lorenz K, Lohse MJ, Hislop JN,…
Development of an Indole-Amide-Based Photoswitchable Cannabinoid Receptor Subtype 1 (CB1R) "Cis-On" Agonist
https://doi.org/10.1021/acschemneuro.2c00160
Archives of Toxicology, Vol. 96, No. 8, 2022, P. 2341-2360
Merches K, Breunig L, Fender J, Brand T, Bätz V, Idel S, Kollipara L, Reinders Y, Sickmann A, Mally A, Lorenz K.
The potential of remdesivir to affect function, metabolism and proliferation of cardiac and kidney cells in vitro
https://doi.org/10.1007/s00204-022-03306-1
Frontiers in Pharmacology, Vol. 13, 2022, P. 962763
Tolstik E, Gongalsky MB, Dierks J, Brand T, Pernecker M, Pervushin NV, Maksutova DE, Gonchar KA, Samsonova JV, Kopeina G, Sivakov V, Osminkina L,…
Raman and fluorescence micro-spectroscopy applied for the monitoring of sunitinib-loaded porous silicon nanocontainers in cardiac cells
https://doi.org/10.3389/fphar.2022.962763
Proceedings of the National Academy of Sciences of the United States of America, Vol. 119, No. 25, 2022, P. e2121867119
Lee J, Olivieri C, Ong C, Masterson LR, Gomes S, Lee B, Schaefer F, Lorenz K, Veglia G, Rosner MR.
Raf Kinase Inhibitory Protein regulates the cAMP-dependent protein kinase signaling pathway through a positive feedback loop
https://doi.org/10.1073/pnas.2121867119
International Journal of Molecular Science, Vol. 23, No. Special Issue , 2022
Tolstik E, Ali N, Guo S, Ebersbach P, Möllmann D, Arias Loza A, Dierks J, Schuler I, Freier E, Debus J, Baba HA, Nordbeck P, Bocklitz T, Lorenz K.
CARS Imaging Advances Early Diagnosis of Cardiac Manifestation of Fabry Disease
https://doi.org/doi: 10.3390/ijms23105345
Cancers, Vol. 14, No. 4, 2022
Lorenz K, Rosner MR.
Harnessing RKIP to Combat Heart Disease and Cancer
http://10.3390/cancers14040867
Cardiovascular Research, Vol. 118, No. 14, 2021, P. 2932-2945
Gil-Pulido J, Amézaga N, Jorgacevic I, Manthey HD, Rösch M, Brand T, Cidlinsky P, Schäfer S, Beilhack A, Saliba A, Lorenz K, Boon L, Prinz I, Waisman…
Interleukin-23 receptor expressing γδ T cells locally promote early atherosclerotic lesion formation and plaque necrosis in mice
https://doi.org/10.1093/cvr/cvab359
International Journal of Molecular Sciences, Vol. 23, No. 2, 2022
Schanbacher C, Bieber M, Reinders Y, Cherpokova D, Mathejka C, Nieswandt B, Sickmann A, Kleinschnitz C, Langhauser F, Lorenz K.
ERK1/2 Activity Is Critical for the Outcome of Ischemic Stroke
Frontiers in Cardiovascular Medicine, Vol. 8, 2021
Kerp H, Hönes GS, Tolstik E, Hönes-Wendland J, Gassen J, Moeller LC, Lorenz K, Führer D.
Protective Effects of Thyroid Hormone Deprivation on Progression of Maladaptive Cardiac Hypertrophy and Heart Failure
https://doi.org/10.3389/fcvm.2021.683522
IJC Heart & Vasculature, Vol. 34, 2021, P. 100781
Pfeiffer J, Lorenz K.
Murine models for heart failure: Their creation and applicability to human still require critical and careful considerations
https://doi.org/10.1016/j.ijcha.2021.100781
ACS Chemical Neuroscience, Vol. 12, No. 9, 2021, P. 1632-1647
Rodríguez-Soacha DA, Fender J, Ramírez YA, Collado JA, Muñoz E, Maitra R, Sotriffer C, Lorenz K, Decker M.
"Photo-Rimonabant": Synthesis and Biological Evaluation of Novel Photoswitchable Molecules Derived from Rimonabant Lead to a Highly Selective and Nanomolar " Cis-On" CB 1 R Antagonist: Synthesis and Biological Evaluation of Novel Photoswitchable Molecules Derived from Rimonabant Lead to a Highly Selective and Nanomolar "Cis-On" CB1R Antagonist
https://doi.org/10.1021/acschemneuro.1c00086
International Journal of Molecular Sciences, Vol. 22, No. 9, 2021
Wagner M, Sadeck MS, Dybkova N, Mason FE, Klehr J, Firneburg R, Cachorro E, Richter K, Klapproth E, Künzel S, Lorenz K, Heijman J, Dobrev D,…
Cellular Mechanisms of the Anti-Arrhythmic Effect of Cardiac PDE2 Overexpression
https://doi.org/10.3390/ijms22094816
Redox Biology, Vol. 41, 2021
Rhoden A, Friedrich FW, Brandt T, Raabe J, Schweizer M, Meisterknecht J, Wittig I, Ulmer BM, Klampe B, Uebeler J, Piasecki A, Lorenz K, Eschenhagen…
Sulforaphane exposure impairs contractility and mitochondrial function in three-dimensional engineered heart tissue
https://doi.org/10.1016/j.redox.2021.101951