Heart Failure & Remodeling

Heart failure is a complex clinical syndrome with a multifaceted pathophysiology. It is a severe condition resulting from ventricular dysfunction, and its prevalence is increasing. Estimated 64 million people worldwide suffer from heart failure. In addition, heart failure is the leading cause of hospitalization in the world. Despite the best available therapies, many patients with heart failure still have a poor prognosis, creating an unmet clinical need for novel therapeutic approaches in heart failure.

Therefore, one of our research interests is to study cardiac remodeling. Maladaptive remodeling is often followed by ventricular dysfunction and subsequent cardiac heart failure and death. In particular, we focus on the function of non-coding RNAs (especially microRNAs, long non-coding RNAs and circular RNAs) in various cardiovascular diseases that cause adverse cardiac remodeling (e.g. pressure overload-induced left ventricular cardiac remodeling). Non-coding RNAs are novel therapeutic targets as critical regulators of gene expression, controlling many physiological and pathological processes. Our primary focus is the development of synthetic RNA-based therapeutics targeting specific non-coding RNAs as a revolutionary pharmacological tool to combat cardiovascular diseases.

Key references:

Abbas N, Haas JA, Xiao K, Fuchs M, Just A, Pich A, Perbellini F, Werlein C, Ius F, Ruhparwar A, Fiedler J, Weber N, Thum T. (2024). Inhibition of miR-21: cardioprotective effects in human failing myocardium ex vivo. European heart journal 45(22), 2016–2018. https://doi.org/10.1093/eurheartj/ehae102

Bauersachs J, Solomon SD, Anker SD, Antorrena-Miranda I, Batkai S, Viereck J, Rump S, Filippatos G, Granzer U, Ponikowski P, de Boer RA, Vardeny O, Hauke W, Thum T. (2024) Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: Rationale and design of the HF-REVERT trial. European journal of heart failure, 26(3), 674–682. https://doi.org/10.1002/ejhf.3139

Lu D, Chatterjee S, Xiao K, Riedel I, Huang CK, Costa A, Cushman S, Neufeldt D, Rode L, Schmidt A, Juchem M, Leonardy J, Büchler G, Blume J, Gern OL, Kalinke U, Wen Tan WL, Foo R, Vink A, van Laake LW, van der Meer P, Bär C, Thum T. (2022) A circular RNA derived from the insulin receptor locus protects against doxorubicin-induced cardiotoxicity. European heart journal, 43(42), 4496–4511. https://doi.org/10.1093/eurheartj/ehac337

Täubel J, Hauke W, Rump S, Viereck J, Batkai S, Poetzsch J, Rode L, Weigt H, Genschel C, Lorch U, Theek C, Levin AA, Bauersachs J, Solomon SD, Thum T. (2021) Novel antisense therapy targeting microRNA-132 in patients with heart failure: results of a first-in-human Phase 1b randomized, double-blind, placebo-controlled study. European heart journal, 42(2), 178–188. https://doi.org/10.1093/eurheartj/ehaa898

Batkai S, Genschel C, Viereck J, Rump S, Bär C, Borchert T, Traxler D, Riesenhuber M, Spannbauer A, Lukovic D, Zlabinger K, Hašimbegović E, Winkler J, Garamvölgyi R, Neitzel S, Gyöngyösi M, Thum T. (2021) CDR132L improves systolic and diastolic function in a large animal model of chronic heart failure. European heart journal, 42(2), 192–201. https://doi.org/10.1093/eurheartj/ehaa791

Foinquinos A, Batkai S, Genschel C, Viereck J, Rump S, Gyöngyösi M, Traxler D, Riesenhuber M, Spannbauer A, Lukovic D, Weber N, Zlabinger K, Hašimbegović E, Winkler J, Fiedler J, Dangwal S, Fischer M, de la Roche J, Wojciechowski D, Kraft T, Garamvölgyi R, Neitzel S, Chatterjee S, Yin X, Bär C, Mayr M, Xiao K, Thum T. (2020) Preclinical development of a miR-132 inhibitor for heart failure treatment. Nature communications, 11(1), 633. https://doi.org/10.1038/s41467-020-14349-2

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