Nichtkodierende RNA-abhängige Therapiestrategien für die Doxorubicin-induzierte Kardiotoxizität
Zusammenfassung der Projektergebnisse
Cancer survivors very often face cardiovascular problems due to cardiotoxic effects of cancer treatments. Chemotherapy drug doxorubicin has been shown to exert dose-dependent cardiotoxicity and induce heart-failure. Aim of my proposal was to identify new therapeutic targets to treat doxorubicin-induced cardiotoxicity. I identified two new targets, a RNA-binding protein and a microRNA cluster which can prevent doxorubicin-induced cardiotoxicity. In independent studies using mouse model of doxorubicin-induced cardiotoxicity, I show that AAV9 mediated cardiac overexpression of RNA-binding protein or microRNA cluster can prevent detrimental effects of doxorubicin and improve cardiac function. Thus, I identified two new potential candidates capable of preventing doxorubicin-induced cardiotoxicity in a pre-clinical mouse model.
Projektbezogene Publikationen (Auswahl)
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Non-coding RNAs as orchestrators of autophagic processes. J Mol Cell Cardiol. 2016 Jun; 95:26-30
Gupta SK, Thum T
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Pre-Clinical Development of a MicroRNA- Based Therapy for Elderly Patients with Myocardial Infarction. J Am Coll Cardiol. 2016 Oct; 68(14):1557-1571
Gupta SK, Foinquinos A, Thum S, Remke J, Zimmer K, Bauters C, de Groote P, Boon RA, de windt LJ, Preissle S, Hein L, Batkai S, Pinet F, Thum T
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Inhibition of the Cardiac Fibroblast-Enriched lncRNA Meg3 Prevents Cardiac Fibrosis and Diastolic Dysfunction. Circ Res. 2017 Aug 18; 121(5):575-583
Piccoli MT, Gupta SK, Viereck J, Foinquinos A, Samolovac S, Kramer FL, Garg A, Remke J, Zimmer K, Batkai S, Thum T
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Quaking inhibits doxorubicin-mediated cardiotoxicity through regulation of cardiac circular RNA expression. Circ Res. 2018 Jan 19;122(2):246-254
Gupta SK, Garg A, Bär C, Chatterjee S, Foinquinos A, Milting H, Streckfuß-Bömeke K, Fiedler J, Thum T
