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| Status |
Public on Jun 12, 2021 |
| Title |
RNA-sequencing explores the transcriptional profile of Wild Type and Fabp3-null mice under physiologicl and cardiac hypertrophic conditions |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Background: Cardiac hypertrophy was accompanied by various cardiovascular diseases (CVDs), due to the high global incidence and mortality of CVDs, it has become increasingly critical to characterize the pathogenesis of cardiac hypertrophy. We aimed to determine the metabolic effects of fatty acid binding protein 3 (FABP3), on transverse aortic constriction (TAC)-induced cardiac hypertrophy. Methods and Results: TAC or Ang II treatment markedly upregulated Fabp3 expression. Notably, Fabp3 ablation aggravated TAC-induced cardiac hypertrophy and cardiac dysfunction. Multi-omics analysis revealed that Fabp3-deficient hearts exhibited disrupted metabolic signatures characterized by increased glycolysis, toxic lipid accumulation, and compromised fatty acid oxidation and ATP production under hypertrophic stimuli. Mechanistically, FABP3 mediated metabolic reprogramming by directly interacting with PPARĪ±, which prevented its degradation and synergistically modulated its transcriptional activity on Mlycd, Gck. Finally, treatment with the PPARĪ± agonist, fenofibrate, rescued the pro-hypertrophic effects of Fabp3 deficiency.
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| Overall design |
Cardiac mRNA from sham or transverse aortic constriction (TAC)-operated WT and Fabp3-null mice were collected for RNA-sequencing analysis, and three independent biological replicates were included in this study.
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| Contributor(s) |
Zhuang L, Liu Z, Li C, Jin Q, Lu L, Tao R, Yan X, Chen K |
| Citation(s) |
34458345 |
| Submission date |
Jun 11, 2021 |
| Last update date |
Aug 31, 2021 |
| Contact name |
Lingfang Zhuang |
| E-mail(s) |
zhuanglingfang@sjtu.edu.cn
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| Phone |
18817288728
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| Organization name |
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
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| Department |
Department of Vascular & Cardiology
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| Lab |
Department of Vascular & Cardiology
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| Street address |
197 Rui Jin Road II
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| City |
Shanghai |
| State/province |
Shanghai |
| ZIP/Postal code |
200025 |
| Country |
China |
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| Platforms (1) |
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| Samples (12)
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| Relations |
| BioProject |
PRJNA736943 |
| SRA |
SRP323718 |
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