ZBED6 identified as a suppressor of pathological cardiac hypertrophy via MEOX1–ERK1/2 and autophagy

Research published in PLOS Genetics by Xiao Zhang, Xiaopeng Liu, Ruirui Pan and colleagues has identified ZBED6, a zinc-finger BED-domain transcription factor previously characterised in the context of skeletal muscle hypertrophy, as a key suppressor of pathological cardiac hypertrophy.

Using myocardial tissue from patients with cardiac hypertrophy alongside cellular and animal models, the authors demonstrate that ZBED6 protein levels are substantially reduced under hypertrophic conditions. Loss of ZBED6 function activates MEOX1, a homeobox transcription factor, which in turn sustains ERK1/2 signalling and disrupts autophagy — the cellular degradation pathway that clears damaged proteins and organelles. The resulting autophagy dysfunction promotes the pathological cell growth that characterises hypertrophic cardiomyopathy.

The study provides mechanistic detail on a previously unexplored transcriptional axis in cardiac disease and positions ZBED6 as a candidate regulatory node in pathological remodelling. The authors caution that the translation of these findings to human therapeutics requires further work; the study is a mechanistic investigation rather than a clinical intervention report. Researchers in cardiovascular genetics and cardiac cell biology will find the MEOX1–ERK1/2–autophagy pathway a tractable target for further investigation.