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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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Assembly of vascular smooth muscle cells in 3D aggregates provokes cellular quiescence. Exp Cell Res. 2020 Mar 1;388(1):111782. doi: 10.1016/j.yexcr.2019.111782. Epub 2019 Dec 16.

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Clusters of cooperative ion channels enable a membrane-potential-based mechanism for short-term memory. Elife. 2020 Feb 7;9. pii: e49974. doi: 10.7554/eLife.49974.

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AAV-mediated TIMP-1 overexpression in aortic tissue reduces the severity of allograft vasculopathy in mice. J Heart Lung Transplant. 2020 Jan 30. pii: S1053-2498(20)31356-5. doi: 10.1016/j.healun.2020.01.1338. [Epub ahead of print]

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Mepivacaine reduces calcium transients in isolated murine ventricular cardiomyocytes. BMC Anesthesiol. 2020 Jan 8;20(1):10. doi: 10.1186/s12871-019-0926-0.

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Factors determining microbial colonization of liquid nitrogen storage tanks used for archiving biological samples. Appl Microbiol Biotechnol. 2020 Jan;104(1):131-144. doi: 10.1007/s00253-019-10242-1. Epub 2019 Nov 28.

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Shaping the heart: Structural and functional maturation of iPSC-cardiomyocytes in 3D-micro-scaffolds. Biomaterials. 2020 Jan;227:119551. doi: 10.1016/j.biomaterials.2019.119551. Epub 2019 Oct 19.

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Simulation Strategies for Calcium Microdomains and Calcium Noise. Adv Exp Med Biol. 2020;1131:771-797. doi: 10.1007/978-3-030-12457-1_31.

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Tyrphostin AG490 reduces inflammation and fibrosis in neonatal obstructive nephropathy. PLoS One. 2019 Dec 17;14(12):e0226675. doi: 10.1371/journal.pone.0226675. eCollection 2019.

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Mild metabolic stress is sufficient to disturb the formation of pyramidal cell ensembles during gamma oscillations. J Cereb Blood Flow Metab. 2019 Dec 16:271678X19892657. doi: 10.1177/0271678X19892657. [Epub ahead of print

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Risk and protective factors for post-thrombotic syndrome after deep venous thrombosis. J Vasc Surg Venous Lymphat Disord. 2019 Dec 13. pii: S2213-333X(19)30537-2. doi: 10.1016/j.jvsv.2019.10.012. [Epub ahead of print]

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AAV-Mediated Expression of AP-1-Neutralizing RNA Decoy Oligonucleotides Attenuates Transplant Vasculopathy in Mouse Aortic Allografts. Mol Ther Methods Clin Dev. 2019 Dec 13;15:246-256. doi: 10.1016/j.omtm.2019.09.009. eCollection 2019 Dec 13. Epub 2019 Oct 2.

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Amyloid, APP, and Electrical Activity of the Brain. Neuroscientist. 2019 Nov 29:1073858419882619. doi: 10.1177/1073858419882619. [Epub ahead of print]

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The mitochondrial calcium uniporter is crucial for the generation of fast cortical network rhythms. J Cereb Blood Flow Metab. 2019 Nov 13:271678X19887777. doi: 10.1177/0271678X19887777. [Epub ahead of print]

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Somatic mutations and promotor methylation of the ryanodine receptor 2 is a common event in the pathogenesis of head and neck cancer. Int J Cancer. 2019 Dec 15;145(12):3299-3310. doi: 10.1002/ijc.32481. Epub 2019 Jun 19.

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Loss of the serine protease HTRA1 impairs smooth muscle cells maturation. Sci Rep. 2019 Dec 3;9(1):18224. doi: 10.1038/s41598-019-54807-6.

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Persistent increase in ventral hippocampal long-term potentiation by juvenile stress: A role for astrocytic glutamine synthetase. Glia. 2019 Dec;67(12):2279-2293. doi: 10.1002/glia.23683. Epub 2019 Jul 17.

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Functional association of a CD40 gene single nucleotide polymorphism with the pathogenesis of coronary heart disease. Cardiovasc Res. 2019 Aug 2. pii: cvz206. doi: 10.1093/cvr/cvz206. [Epub ahead of print]


Institute of
Physiology and Pathophysiology

Heidelberg University

Im Neuenheimer Feld 326

69120 Heidelberg

Germany

Phone:+49 6221 54-4056
Fax:+49 6221 54-6364
E-mail:susanne.bechtel@
physiologie.uni-heidelberg.de