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Institute of Physiology and Pathophysiology

Decoy oligodeoxynucleotides for the prevention of heart failure

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This research field aims at preclinically validating decoy oligodeoxynucleotides (ODNs) as a novel class of therapeutic drugs to prevent or treat heart failure.

    

Decoy ODNs, typically 15 to 20 base pairs short double-stranded DNA molecules, mimic the DNA binding site of specific regulatory proteins (transcription factors) in the genome. They interfere with the, in most cases, aberrant expression of disease-related genes by specifically binding to and, as a consequence, blocking the transcription factor controlling their expression.

 

Three different potential transcription factor drug targets are investigated. The most important criterion for choosing them is their proven involvement in the expression of genes primarily responsible for the development of various forms of terminal heart failure.

 

Members of the Division of Cardiovascular Physiology work on the design and optimization of the respective decoy ODNs. In collaboration with other groups at Heidelberg University  in vitro and in vivo model systems for the evaluation of their efficacy have been developed.

 

   

 

Aggregates of rat cardiomyocytes loaded with fluorescent decoy ODNs (red) (cell nuclei: blue)


Recent Publications

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High-fat diet suppresses the positive effect of creatine supplementation on skeletal muscle function by reducing protein expression of IGF-PI3K-AKT-mTOR pathway. PLoS One. 2018 Oct 4;13(10):e0199728. doi: 10.1371/journal.pone.0199728. eCollection 2018.

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Alcohol reduces muscle fatigue through atomistic interactions with nicotinic receptors. Commun Biol. 2018 Oct 3;1:159. doi: 10.1038/s42003-018-0157-9. eCollection 2018.

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Possible neurotoxicity of the anesthetic propofol: evidence for the inhibition of complex II of the respiratory chain in area CA3 of rat hippocampal slices. Arch Toxicol. 2018 Oct;92(10):3191-3205. doi: 10.1007/s00204-018-2295-8. Epub 2018 Aug 24.

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Endothelial progenitor cells accelerate endothelial regeneration in an in vitro model of Shigatoxin-2a-induced injury via soluble growth factors. Am J Physiol Renal Physiol. 2018 Oct 1;315(4):F861-F869. doi: 10.1152/ajprenal.00633.2017. Epub 2018 Mar 7.

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Strategy for marker-based differentiation of pro- and anti-inflammatory macrophages using matrix-assisted laser desorption/ionization mass spectrometry imaging. Analyst. 2018 Sep 10;143(18):4273-4282. doi: 10.1039/c8an00659h. Epub 2018 Jul 20.

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Early appearance and spread of fast ripples in the hippocampus in a model of cortical traumatic brain injury. J Neurosci. 2018 Sep 6. pii: 3507-17. doi: 10.1523/JNEUROSCI.3507-17.2018. [Epub ahead of print]

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Recent advances in hippocampal structure and function. Cell Tissue Res. 2018 Sep;373(3):521-523. doi: 10.1007/s00441-018-2913-z. Epub 2018 Aug 20. doi: 10.1007/s00441-018-2913-z. Editorial. No abstract available.

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Electrical coupling between hippocampal neurons: contrasting roles of principal cell gap junctions and interneuron gap junctions. Cell Tissue Res. 2018 Sep;373(3):671-691. doi: 10.1007/s00441-018-2881-3. Epub 2018 Aug 15. Review.

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Synaptic entrainment of ectopic action potential generation in hippocampal pyramidal neurons. J Physiol. 2018 Aug 24. doi: 10.1113/JP276720. [Epub ahead of print]

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Metabolic modulation of neuronal gamma-band oscillations. Pflugers Arch2018 Sep;470(9):1377-1389. doi: 10.1007/s00424-018-2156-6. Epub 2018 May 28.

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NFAT5 Isoform C Controls Biomechanical Stress Responses of Vascular Smooth Muscle Cells. Front Physiol. 2018 Aug 23;9:1190. doi: 10.3389/fphys.2018.01190. eCollection 2018.

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Persistent sodium current modulates axonal excitability in CA1 pyramidal neurons. J Neurochem. 2018 Aug;146(4):446-458. doi: 10.1111/jnc.14479. Epub 2018 Aug 1.

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Selective vulnerability of αOFF retinal ganglion cells during onset of autoimmune optic neuritis. Neuroscience. 2018 Jul 31. pii: S0306-4522(18)30515-3. doi: 10.1016/j.neuroscience.2018.07.040. [Epub ahead of print]

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The VAMP-associated protein VAPB is required for cardiac and neuronal pacemaker channel function. FASEB J. 2018 Jun 7:fj201800246R. doi: 10.1096/fj.201800246R. [Epub ahead of print]

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The lncRNA CASC9 and RNA binding protein HNRNPL form a complex and co-regulate genes linked to AKT signaling. Hepatology. 2018 May 23. doi: 10.1002/hep.30102. [Epub ahead of print]


Institute of
Physiology and Pathophysiology

Heidelberg University

Im Neuenheimer Feld 326

69120 Heidelberg

Germany

Phone:+49 6221 54-4035
Fax:+49 6221 54-4038
E-mail:sekretariat.hecker@
physiologie.uni-heidelberg.de