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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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Improving electrical properties of iPSC-cardiomyocytes by enhancing Cx43 expression. J Mol Cell Cardiol. 2018 Jul;120:31-41. doi: 10.1016/j.yjmcc.2018.05.010. Epub 2018 May 16.

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Role of CD40 and ADAMTS13 in von Willebrand factor-mediated endothelial cell-platelet-monocyte interaction. Proc Natl Acad Sci U S A. 2018 Jun 12;115(24):E5556-E5565. doi: 10.1073/pnas.1801366115. Epub 2018 May 23.

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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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Persistent sodium current modulates axonal excitability in CA1 pyramidal neurons. J Neurochem. 2018 Jun 4. doi: 10.1111/jnc.14479. [Epub ahead of print]

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Metabolic modulation of neuronal gamma-band oscillations. Pflugers Arch. 2018 May 28. doi: 10.1007/s00424-018-2156-6. [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]

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Early Blood-Brain Barrier Disruption in Ischemic Stroke Initiates Multifocally Around Capillaries/Venules. Stroke. 2018 Jun;49(6):1479-1487. doi: 10.1161/STROKEAHA.118.020927. Epub 2018 May 14.

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Impact of carbonylation on glutathione peroxidase-1 activity in human hyperglycemic endothelial cells. Redox Biol. 2018 Jun;16:113-122. doi: 10.1016/j.redox.2018.02.018. Epub 2018 Mar 1.

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In silico assessment of the conduction mechanism of the Ryanodine Receptor 1 reveals previously unknown exit pathways. Sci Rep. 2018 May 2;8(1):6886. doi: 10.1038/s41598-018-25061-z.

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Astrocytic glutamine synthetase is expressed in the neuronal somatic layers and down-regulated proportionally to neuronal loss in the human epileptic hippocampus. Glia. 2018 May;66(5):920-933. doi: 10.1002/glia.23292. Epub 2018 Jan 19.

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Parallel detection of theta and respiration-coupled oscillations throughout the mouse brain. Sci Rep. 2018 Apr 24;8(1):6432. doi: 10.1038/s41598-018-24629-z.

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Stability and Function of Hippocampal Mossy Fiber Synapses Depend on Bcl11b/Ctip2. Front Mol Neurosci. 2018 Apr 5;11:103. doi: 10.3389/fnmol.2018.00103. eCollection 2018.

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Glycyrrhetinic Acid Antagonizes Pressure-Induced Venous Remodeling in Mice. Front Physiol. 2018 Apr 4;9:320. doi: 10.3389/fphys.2018.00320. eCollection 2018.

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Respiration-Entrained Brain Rhythms Are Global but Often Overlooked. Trends Neurosci. 2018 Apr;41(4):186-197. doi: 10.1016/j.tins.2018.01.007. Epub 2018 Feb 9.

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Hypertension-evoked RhoA activity in vascular smooth muscle cells requires RGS5. FASEB J. 2018 Apr;32(4):2021-2035. doi: 10.1096/fj.201700384RR. Epub 2018 Jan 5.

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Carnosine Catalyzes the Formation of the Oligo/Polymeric Products of Methylglyoxal. Cell Physiol Biochem. 2018 Apr;46(2):713-726. doi: 10.1159/000488727. Epub 2018 Mar 29.

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Bringing European physiologists together. Acta Physiol (Oxf). 2018 Apr;222(4):e13043. doi: 10.1111/apha.13043. Epub 2018 Feb 15.

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Making room for new memories. Science. 2018 Mar 30;359(6383):1461-1462. doi: 10.1126/science.aat1493.

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VCAM-1 expression is upregulated by CD34+/CD133+-stem cells derived from septic patients. PLoS One. 2018 Mar 30;13(3):e0195064. doi: 10.1371/journal.pone.0195064. eCollection 2018.

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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 Mar 7. doi: 10.1152/ajprenal.00633.2017. [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