ATF4 in cardiovascular diseases: an emerging therapeutic target
Related Experiment Video
Updated: Jan 14, 2026
Precision Ultrasound-guided Stem Cell Delivery for Vascular Repair in Aortic Diseases
Published on: June 20, 2025
Luning Qin1, Ruolan Chen1, Chao Huang2
1Department of Cardiology, the Affiliated Hospital of Qingdao University, No. 59 Haier Road, Qingdao 266100, Shandong, China.
Abstract:
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.
Insights
Activating transcription factor 4 (ATF4) regulates cell fate via endoplasmic reticulum stress and autophagy. Understanding its cardiovascular disease mechanisms could lead to new therapies targeting the ATF4 metabolic-death axis.
Area of Science:
- Molecular Biology
- Cardiovascular Research
- Cellular Stress Response
Background:
- Activating transcription factor 4 (ATF4) is a key regulator in the ATF/CREB family, influencing cell fate through endoplasmic reticulum stress (ERS), autophagy, and redox networks.
- Maintaining cardiovascular homeostasis relies on the balanced function of ATF4, yet its regulatory mechanisms in cardiovascular diseases (CVDs) are not fully understood.
Purpose of the Study:
- To systematically elucidate the dynamic regulatory network of ATF4 in cardiovascular diseases (CVDs).
- To construct an interaction map of ATF4.
- To identify critical research areas for advancing ATF4-targeted CVD therapies.
Main Methods:
- Systematic elucidation of ATF4 regulatory networks.
- Construction of ATF4 interaction maps.
- Identification of key research gaps and future directions.
Main Results:
- The study outlines the complex regulatory network of ATF4 in the context of CVDs.
- An interaction relationship map for ATF4 has been constructed.
- Three critical research areas were highlighted: cell-type-specific epigenetic regulation, spatiotemporally specific ATF4 activation strategies, and tissue-targeted ATF4 modulators.
Conclusions:
- Further research into ATF4's cell-type-specific epigenetic regulation, precise intervention strategies, and targeted modulators is crucial.
- Advancements in these areas are expected to yield novel therapeutic strategies for CVDs by targeting the ATF4-mediated metabolic-death axis.
More Related Videos
Related Concept Videos
01:26Atherosclerosis III: Management
01:26Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:27Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
01:30Atherosclerosis I: Introduction