ATF4 in cardiovascular diseases: an emerging therapeutic target

Activating transcription factor 4 (ATF4), as a core regulatory factor of the activating transcription factor (ATF)/cAMP-response element binding protein (CREB) family, governs cell fate determination through endoplasmic reticulum stress(ERS), autophagy, and redox networks. The dynamic balance of its functions is crucial for maintaining cardiovascular homeostasis; however, there remains a significant lack of systematic understanding of its regulatory mechanisms. To address the aforementioned research gap, this article systematically elucidates the dynamic regulatory network of ATF4 in cardiovascular diseases (CVDs), constructs its interaction relationship map, and highlights three critical scientific issues that urgently need to be resolved: the cell-type-specific epigenetic regulatory network of ATF4, precise intervention strategies for spatiotemporally specific ATF4 activation, and the development of tissue-targeted ATF4 modulators. Breakthroughs in these research directions are expected to provide novel therapeutic strategies for CVDs targeting the ATF4-mediated metabolic-death axis.