| First Author | Li J | Year | 2023 |
| Journal | J Am Heart Assoc | Volume | 12 |
| Issue | 17 | Pages | e028185 |
| PubMed ID | 37642020 | Mgi Jnum | J:342509 |
| Mgi Id | MGI:7538224 | Doi | 10.1161/JAHA.122.028185 |
| Citation | Li J, et al. (2023) TRAF Family Member 4 Promotes Cardiac Hypertrophy Through the Activation of the AKT Pathway. J Am Heart Assoc 12(17):e028185 |
| abstractText | Background Pathological cardiac hypertrophy is a major cause of heart failure morbidity. The complex mechanism of intermolecular interactions underlying the pathogenesis of cardiac hypertrophy has led to a lack of development and application of therapeutic methods. Methods and Results Our study provides the first evidence that TRAF4, a member of the tumor necrosis factor receptor-associated factor (TRAF) family, acts as a promoter of cardiac hypertrophy. Here, Western blotting assays demonstrated that TRAF4 is upregulated in cardiac hypertrophy. Additionally, TRAF4 deletion inhibits the development of cardiac hypertrophy in a mouse model after transverse aortic constriction surgery, whereas its overexpression promotes phenylephrine stimulation-induced cardiomyocyte hypertrophy in primary neonatal rat cardiomyocytes. Mechanistically, RNA-seq analysis revealed that TRAF4 promoted the activation of the protein kinase B pathway during cardiac hypertrophy. Moreover, we found that inhibition of protein kinase B phosphorylation rescued the aggravated cardiomyocyte hypertrophic phenotypes caused by TRAF4 overexpression in phenylephrine-treated neonatal rat cardiomyocytes, suggesting that TRAF4 may regulate cardiac hypertrophy in a protein kinase B-dependent manner. Conclusions Our results revealed the regulatory function of TRAF4 in cardiac hypertrophy, which may provide new insights into developing therapeutic and preventive targets for this disease. |
