TRIM26 exacerbates pathological cardiac hypertrophy by activating TAK1.

Area of Science:

• Cardiovascular Biology
• Molecular Cardiology
• Pathogenesis of Heart Failure

Background:

• Pathological myocardial hypertrophy is a major cause of heart failure.
• Understanding the molecular mechanisms underlying cardiac hypertrophy is crucial for developing effective treatments.

Purpose of the Study:

• To investigate the role of Tripartite motif-containing 26 (TRIM26) in pathological cardiac hypertrophy.
• To elucidate the molecular pathway through which TRIM26 exerts its effects.

Main Methods:

• Generated Trim26 global knockout mice and TRIM26 overexpression adenoviruses.
• Utilized transverse aortic constriction (TAC) surgery and phenylephrine (PE) stimulation in mice and neonatal rat cardiomyocytes (NRCMs).
• Employed RNA sequencing and molecular biology techniques to identify TRIM26 targets and signaling pathways.

Main Results:

• TRIM26 expression was upregulated in response to hypertrophic stimuli.
• Trim26 deletion attenuated cardiac hypertrophy, inflammation, fibrosis, and dysfunction.
• TRIM26 overexpression exacerbated cardiomyocyte hypertrophy and inflammation, while knockdown had opposing effects.
• TRIM26 was found to activate the transforming growth factor-beta activated kinase 1 (TAK1)-c-Jun N-terminal kinase/p38 signaling pathway.

Conclusions:

• TRIM26 plays a significant role in promoting pathological cardiac hypertrophy.
• The TRIM26-TAK1 signaling axis is a key mediator of cardiac hypertrophy.
• Targeting the TRIM26-TAK1 pathway presents a potential therapeutic strategy for pathological cardiac hypertrophy and heart failure.