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| Status |
Public on Nov 17, 2024 |
| Title |
Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction [control vs HF] |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Myocardial fibrosis leads to cardiac dysfunction and arrhythmias in heart failure with preserved ejection fraction (HFpEF), but the underlying mechanisms remain poorly understood. Here, RNA sequencing identifies Forkhead Box1 (FoxO1) signaling as abnormal in HFpEF hearts. Genetic suppression of FoxO1 alters the intercellular communication between cardiomyocytes and fibroblasts, alleviates abnormal diastolic relaxation, and reduces arrhythmias. Targeted downregulation of FoxO1 in activated fibroblasts reduces cardiac fibrosis, blunts arrhythmogenesis and improves diastolic function in HFpEF. These results not only implicate FoxO1 in arrhythmogenesis and lusitropy but also demonstrate that pro-fibrotic cardiomyocyte-fibroblast communication can be corrected, constituting a novel therapeutic strategy for HFpEF.
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| Overall design |
RNA sequencing from left ventricular tissue was performed to identify transcriptomic changes in C56Bl6 fed with a standard diet (control), High-Fat + L-NAME diet treated with AAV-scramble-sh (HFpEF-scr), and High-Fat + L-NAME diet treated with AAV-FoxO1-sh (HFpEF-FoxO1-sh).
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| Contributor(s) |
Mesquita T, Cingolani E |
| Citation missing |
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| Submission date |
Aug 08, 2023 |
| Last update date |
Nov 17, 2024 |
| Contact name |
Thassio Mesquita |
| E-mail(s) |
[email protected]
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| Organization name |
Cedars-Sinai Medical Center
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| Department |
Smidt Heart Institute
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| Street address |
8700 Beverly Boulevard
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| City |
Los Angeles |
| State/province |
California |
| ZIP/Postal code |
90048 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (14)
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| This SubSeries is part of SuperSeries: |
| GSE240404 |
Upregulated FoxO1 promotes arrhythmogenesis in mice with heart failure and preserved ejection fraction |
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| Relations |
| BioProject |
PRJNA1003514 |
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