Skip to content

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