Heart failure & cardiomyopathies
Targeting Transmembrane BAX Inhibitor Motif Containing 1 Alleviates Pathological Cardiac Hypertrophy
Authors' conclusion
TMBIM1 protects against pathological cardiac hypertrophy through promoting the lysosomal degradation of activated TLR4.
Study context
- Population
- Patients with HF and mice with aortic banding (AB)-induced cardiac hypertrophy; monkey AB model
Main finding
As reported in the abstract
- TMBIM1 expression significantly downregulated on hypertrophic stimuli in human and mouse hearts
- Cardiac Tmbim1 silencing aggravated AB-induced cardiac hypertrophy; blunted by Tmbim1 overexpression
- TLR4 signalling pathway disrupted dramatically by Tmbim1 manipulation
- Effects of TMBIM1 on cardiac hypertrophy dependent on TLR4 (double-knockout mice)
- TMBIM1 promoted lysosome-mediated degradation of activated TLR4
- TMBIM1 directly interacted with tumor susceptibility gene 101 via a PTAP motif and accelerated formation of multivesicular bodies delivering TLR4 to lysosomes
- Lentivirus-mediated TMBIM1 overexpression reversed AB-induced cardiac hypertrophy in monkeys
Original publication
Targeting Transmembrane BAX Inhibitor Motif Containing 1 Alleviates Pathological Cardiac Hypertrophy. Circulation. Published 11 December 2017. doi:10.
Summarised from the published abstract; every number is checked against it