CARDINAL - Cardiomyocyte-derived vesicular non coding RNAs and post-ischemic cardiac remodeling
Endocrinology, Diabetology, Metabolism
Final Report Abstract
Molecular signaling in the ischemic myocardium is a tightly controlled process at the intracellular level. The knowledge on extracellular-mediated cardiac remodeling is very limited and needs further investigations. We aimed to decipher the contribution of cardiomyocyte-derived extracellular vesicles towards myocardial ischemia. Applying high-troughput content analysis of purified vesicle subtypes revealed the loading of specific lncRNAs during cardiomyocyte hypoxia in vitro. Especially lncRNA NEAT1 was identified and described to impact on cellular homeostasis both for cardiomyocytes and cardiac fibroblasts. Genetic loss of murine NEAT1 led to impaired cardiac remodeling after ischemic myocardial injury and thereby underlines its key function for cardiac repair and healing. Therapeutic interventions should thus aim to maintain myocardial NEAT1 expression, e.g. via the modulation of transcription factors or via the activation of signaling cascades by small molecules.
Publications
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(2019) RNA-based diagnostic and therapeutic strategies for cardiovascular disease. Nat Rev Cardiol. 2019 Jun 11
Lu D, Thum T
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(2019). Long Noncoding RNA-Enriched Vesicles Secreted by Hypoxic Cardiomyocytes Drive Cardiac Fibrosis. Mol Ther Nucleic Acids. 2019 Sep 13;18:363-374
Kenneweg F, Bang C, Xiao K, Boulanger CM, Loyer X, Mazlan S, Schroen B, Hermans- Beijnsberger S, Foinquinos A, Hirt MN, Eschenhagen T, Funcke S, Stojanovic S, Genschel C, Schimmel K, Just A, Pfanne A, Scherf K, Dehmel S, Raemon-Buettner SM, Fiedler J, Thum T
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Preclinical and Clinical Development of Noncoding RNA Therapeutics for Cardiovascular Disease. Circ Res. 2020 Feb 28;126(5):663-678
Huang CK, Kafert-Kasting S, Thum T
