TANK Promotes Pressure Overload Induced Cardiac Hypertrophy via Activating AKT Signaling Pathway

• Main Authors: Yanan Pang, Minglu Ma, Dong Wang, Xun Li, Li Jiang
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2021-09-01
• Series: Frontiers in Cardiovascular Medicine
• Subjects: TRAF family member associated NF-κB activator; AKT signal pathway; scaffold protein; pathological cardiac hypertrophy; tansgenic mice
• Online Access: https://www.frontiersin.org/articles/10.3389/fcvm.2021.687540/full

Background: TANK (TRAF family member associated NF-κB activator) acts as a member of scaffold proteins participated in the development of multiple diseases. However, its function in process of cardiac hypertrophy is still unknown.Methods and Results: In this study, we observed an increased expression of TANK in murine hypertrophic hearts after aortic banding, suggesting that TANK may be involved in the pathogenesis of cardiac hypertrophy. We generated cardiac-specific TANK knockout mice, and subsequently subjected to aortic banding for 4–8 weeks. TANK knockout mice showed attenuated cardiac hypertrophy and dysfunction compared to the control group. In contrast, cardiac-specific TANK transgenic mice showed opposite signs. Consistently, in vitro experiments revealed that TANK knockdown decreased the cell size and expression of hypertrophic markers. Mechanistically, AKT signaling was inhibited in TANK knockout mice, but activated in TANK transgenic mice after aortic banding. Blocking AKT signaling with a pharmacological AKT inhibitor alleviated the cardiac hypertrophy and dysfunction in TANK transgenic mice.Conclusions: Collectively, we identified TANK accelerates the progression of pathological cardiac hypertrophy and is a potential therapeutic target.