Abstract P2044: The Cardioprotective Egr-1 And Maladaptive Sp-1 Zinc Finger Transcription Factor Reciprocally Regulates Expression Of The Cardiomyocyte Performance Enhancing Protein S100a1

• Published in: Circulation research 2022-08, Vol.131 (Suppl_1), p.AP2044-AP2044
• Main Authors: Busch, Martin, Bui, Thien-Kim, Adrian, Lukas, Guenther, Fabian, Rettel, Mandy, Stein, Frank, Haas, Jan, Klett, Hagen, Boerries, Melanie, Meder, Benjamin, Dieterich, Christoph, Katus, Hugo A, Most, Patrick
• Format: Article
• Language: English
• ISSN: 0009-7330; 1524-4571
• DOI: 10.1161/res.131.suppl_1.P2044

Background and HypothesisExpression of the cardiomyocyte (CM) protein S100A1, which improves contractile performance of the heart, sharply increases during postnatal myocardial maturation but declines rapidly in failing hearts. We therefore hypothesized that CMs are wired with transcriptional factors (TFs) that positively and negatively regulate S100A1’s gene locus activity. Understanding these reciprocal circuits may be relevant for advanced therapeutic modulation of S100A1’s abundance in diseased hearts. Methods and ResultsH9C2 rat cardiomyoblasts, an animal-free in vitro tool, displayed a strong concordant rise in S100A1 mRNA and protein levels (8.1+/-1.1 vs. cont.; n=9, p2-fold enrichment over control were selected delivering EGR1 and SP1 as top hits. Subsequent siRNA-mediated silencing of both TFs yielded an EGR1 and SP1 knock-down dose-dependent inhibition (80%; p