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.
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Molecular Metabolism, Vol. 79, 2023, P. 101859
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Mutations in DNAJC19 cause altered mitochondrial structure and increased mitochondrial respiration in human iPSC-derived cardiomyocytes
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Chemistry-A European Journal, Vol. 30, No. 11, 2023, P. e202303506
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"Photo-Adrenalines": ß2-Adrenergic Receptor Agonists as Molecular Probes for the Study of Spatiotemporal Adrenergic Signaling
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Cells, Vol. 12, No. 13, 2023, P. 1780
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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
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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
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CNP Promotes Antiarrhythmic Effects via Phosphodiesterase 2
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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
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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
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
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
FEBS open bio, Vol. 10, No. 7, 2020, P. 1210-1218
Künzel SR, Rausch JSE, Schäffer C, Hoffmann M, Künzel K, Klapproth E, Kant T, Herzog N, Küpper J, Lorenz K, Dudek S, Emig R, Ravens U, Rog-Zielinska…
Modeling atrial fibrosis in vitro - Generation and characterization of a novel human atrial fibroblast cell line
https://doi.org/10.1002/2211-5463.12896
Nature Communications, Vol. 11, No. 1, 2020
Tomasovic A, Brand T, Schanbacher C, Kramer S, Hümmert MW, Godoy P, Schmidt-Heck W, Nordbeck P, Ludwig J, Homann S, Wiegering A, Shaykhutdinov T,…
Interference with ERK-dimerization at the nucleocytosolic interface targets pathological ERK1/2 signaling without cardiotoxic side-effects
https://doi.org/10.1038/s41467-020-15505-4
Biochemical and Biophysical Research Communications, Vol. 520, No. 2, 2019, P. 327-332
Maimari T, Krasel C, Bünemann M, Lorenz K.
The N-termini of GRK2 and GRK3 simulate the stimulating effects of RKIP on β-adrenoceptors
https://doi.org/10.1016/j.bbrc.2019.09.135
ESC heart failure, Vol. 6, No. 5, 2019, P. 1015-1026
Jochmann S, Elkenani M, Mohamed BA, Buchholz E, Lbik D, Binder L, Lorenz K, Shah AM, Hasenfuß G, Toischer K, Schnelle M.
Assessing the role of extracellular signal-regulated kinases 1 and 2 in volume overload-induced cardiac remodelling
https://doi.org/10.1002/ehf2.12497
International Journal of Molecular Sciences, Vol. 20, No. 9, 2019
Breitenbach T, Lorenz K, Dandekar T.
How to Steer and Control ERK and the ERK Signaling Cascade Exemplified by Looking at Cardiac Insufficiency
https://doi.org/10.3390/ijms20092179
Clinical pharmacology and therapeutics, Vol. 2019, No. 5, 2018, P. 1224-1233
Müntze J, Gensler D, Maniuc O, Liu D, Cairns T, Hu K, Lorenz K, Frantz S, Wanner C, Nordbeck P.
Oral Chaperone Therapy Migalastat for Treating Fabry Disease: Enzymatic Response and Serum Biomarker Changes After 1 Year
https://doi.org/10.1002/cpt.1321
Magnetic Resonance in Medicine, Vol. 0, No. 0, 2018
Gensler D, Salinger T, Düring M, Lorenz K, Jahns R, Wech T, Frantz S, Ertl G, Jakob PM, Nordbeck P.
Real-time Triggered RAdial Single-Shot Inversion recovery for arrhythmia-insensitive myocardial T1 mapping: motion phantom validation and in vivo comparison.
https://doi.org/10.1002/mrm.27526
Cardiology Research and Practice, Vol. 2018, No. Article ID 3713897, 2018, P. 1-7
Salinger T, Hu K, Liu D, Taleh S, Herrmann S, Oder D, Gensler D, Müntze J, Ertl G, Lorenz K, Frantz S, Weidemann F, Nordbeck P.
Association between Comorbidities and Progression of Transvalvular Pressure Gradients in Patients with Moderate and Severe Aortic Valve Stenosis
https://doi.org/10.1155/2018/3713897
Molecular aspects of medicine, Vol. 63, 2018, P. 47-58
Cuello F, Wittig I, Lorenz K, Eaton P.
Oxidation of cardiac myofilament proteins: Priming for dysfunction?
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PLOS One, Vol. 13, No. 8, 2018
Koussémou M, Lorenz K, Klotz K.
The A2B adenosine receptor in MDA-MB-231 breast cancer cells diminishes ERK1/2 phosphorylation by activation of MAPK-phosphatase-1
https://doi.org/10.1371/journal.pone.0202914
Skeletal Muscle, Vol. 8, No. 28, 2018
Coraspe JAG, Weis J, Anderson ME, Münchberg U, Lorenz K, Buchkremer S, Carr S, Zahedi R, Brauers E, Michels H, Sunada Y, Lochmüller H, Campbell KP,…
Biochemical and pathological changes result from mutated Caveolin-3 in muscle
https://doi.org/10.1186/s13395-018-0173-y
Circulation Cardiovascular Imaging, Vol. 11, No. 8, 2018
Herrmann S, Fries B, Salinger T, Liu D, Hu K, Gensler D, Strotmann J, Christa M, Beer M, Gattenlöhner S, Störk S, Voelker W, Bening C, Lorenz K, Leyh…
Myocardial Fibrosis Predicts 10-Year Survival in Patients Undergoing Aortic Valve Replacement
https://doi.org/10.1161/CIRCIMAGING.117.007131
FASEB Journal, Vol. Volume 32, No. No. 5, 2018
Neumann V, Knies R, Seidinger A, Simon A, Lorenz K, Matthey M, Breuer J, Wenzel D.
The β2 agonist terbutaline specifically decreases pulmonary arterial pressure under normoxia and hypoxia via α adrenoceptor antagonism
https://doi.org/10.1096/fj.201700684RR
Scientific reports, Vol. 8, 2018
Joos J, Staadatmand A, Schnabel C, Viktorinova I, Brand T, Kramer M, Nattel S, Dobrev D, Tomancak P, Backs J, Kleinbongard P, Heusch G, Lorenz K,…
Ectopic expression of S28A-mutated Histone H3 modulates longevity, stress resistance and cardiac function in Drosophila
https://doi.org/10.1038/s41598-018-21372-3
Cardiovascular Research, Vol. 114, No. 5, 2018, P. 641-642
Dobrev D, Lorenz K.
Age-dependent increase in c-Jun N-terminal kinase-2 activity: does this help to understand Ca2+-calmodulin-dependent protein-kinase II-mediated atrial arrhythmogenesis in human atrial fibrillation?
https://doi.org/10.1093/cvr/cvy037
Proceedings of the National Academy of Sciences of the United States of America, Vol. 114, No. 51, 2017
Skinner J, Wang S, Lee J, Ong C, Sommese R, Sivaramakrishnan S, Koelmel W, Hirschbeck M, Schindelin H, Kisker C, Lorenz K, Sosnick TR, Rosner MR.
A conserved salt bridge competition triggered by phosphorylation regulates the protein interactome
Thrombosis and Haemostasis, Vol. 117, No. 1, 2016, P. 176-187
Vorlova S, Koch M, Manthey HD, Cochain C, Busch M, Chaudhari SM, Stegner D, Yepes M, Lorenz K, Nolte MW, Nieswandt B, Zernecke A.
Coagulation factor XII induces pro-inflammatory cytokine responses in macrophages and promotes atherosclerosis in mice
https://doi.org/10.1160/TH16-06-0466
Circulation: Cardiovascular Genetics, Vol. 10, No. 5, 2016
Oder D, Liu D, Hu K, Üçeyler N, Salinger T, Müntze J, Lorenz K, Kandolf R, Gröne H, Sommer C, Ertl G, Wanner C, Nordbeck P.
α-Galactosidase A Genotype N215S Induces a Specific Cardiac Variant of Fabry Disease
https://doi.org/10.1161/CIRCGENETICS.116.001691
BMC Cardiovascular Disorders , Vol. 8, No. 7, 2016, P. 11950-11962
Salinger T, Hu K, Liu D, Herrmann S, Lorenz K, Ertl G, Nordbeck P.
Cardiac amyloidosis mimicking severe aortic valve stenosis - a case report demonstrating diagnostic pitfalls and role of dobutamine stress echocardiography
https://doi.org/10.1186/s12872-017-0519-0
Oncotarget, Vol. 8, No. 7, 2017, P. 11950-11962
Pott LL, Hagemann S, Reis H, Lorenz K, Bracht T, Herold T, Skryabin BV, Megger DA, Kälsch J, Weber F, Sitek B, Baba HA.
Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC
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Circulation Research, Vol. 120, No. 1, 2016, P. 120-132
Vettel C, Lindner M, Dewenter M, Lorenz K, Schanbacher C, Riedel M, Lämmle S, Meinecke S, Mason FE, Sossalla S, Geerts A, Hoffmann M, Wunder F,…
Phosphodiesterase 2 Protects Against Catecholamine-Induced Arrhythmia and Preserves Contractile Function After Myocardial Infarction
https://doi.org/10.1161/CIRCRESAHA.116.310069
Basic Research in Cardiology, Vol. 111, No. 66, 2016, P. 1-4
Cuello F, Lorenz K.
Inhibition of cardiac CaMKII to cure heart failure: Step by step towards translation?
https://doi.org/10.1007/s00395-016-0582-1
Molecular bioSystems, Vol. 12, No. 8, 2016, P. 2436-2446
Brietz A, Schuch KV, Wangorsch G, Lorenz K, Dandekar T.
Analyzing ERK 1/2 signalling and targets
https://doi.org/10.1039/C6MB00255B
Frontiers in Pharmacology, Vol. 7, 2016, P. 118
Propping S, Lorenz K, Michel MC, Wirth MP, Ravens U.
β-Adrenoceptor-mediated Relaxation of Urinary Bladder Muscle in β2-Adrenoceptor Knockout Mice
https://doi.org/10.3389/fphar.2016.00118
Biochemistry, Vol. 55, No. 12, 2016, P. 1909-1917
McReynolds AC, Karra AS, Li Y, Lopez ED, Turjanski AG, Dioum E, Lorenz K, Zaganjor E, Stippec S, McGlynn K, Earnest S, Cobb MH.
Phosphorylation or Mutation of the ERK2 Activation Loop Alters Oligonucleotide Binding
https://doi.org/10.1021/acs.biochem.6b00096