Our results show that 4-HNE directly binds to VCP and disrupts its signaling pathway, induces ubiquitination accumulation, which ultimately leads to cardiomyocyte death, providing a new mechanism for the cardiac injury of 4-HNE. Meanwhile, metformin effectively alleviates 4-HNE induced ubiquitination and cell death in cardiomyocytes and diabetic cardiomyopathy models, and improves cardiac function, demonstrating potential therapeutic effects.
Liang et al. (Sat,) studied this question.