Abstract
Atherosclerosis, the pathophysiological basis of most malignant cardiovascular diseases, remains a global concern. Transcription factors play a key role in regulating cell function and disease progression in developmental signaling pathways involved in atherosclerosis. Activated transcription factor (ATF) 3 is an adaptive response gene in the ATF/cAMP response element binding (CREB) protein family that acts as a transcription suppressor or activator by forming homodimers or heterodimers with other ATF/CREB members. Appropriate ATF3 expression is vital for normal physiological cell function. Notably, ATF3 exhibits distinct roles in vascular endothelial cells, macrophages, and the liver, which will also be described in detail. This review provides a new perspective for atherosclerosis therapy by summarizing the mechanism of ATF3 in atherosclerosis, as well as the structure and pathophysiological properties of ATF3.
Key messages
• In endothelial cells, ATF3 overexpression aggravates oxidative stress and inflammation.
• In macrophages and liver cells, ATF3 can act as a negative regulator of inflammation and promote cholesterol metabolism.
• ATF3 can be used as a potential therapeutic factor in the treatment of atherosclerosis.
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Abbreviations
- ALK:
-
Activin receptor-like kinase
- ATF:
-
Activated transcription factor
- Ang II:
-
Angiotensin II
- ACE2:
-
Angiotensin-converting enzyme 2
- AS:
-
Atherosclerosis
- bZip:
-
Basic region leucine zipper
- cAMP:
-
Cyclic adenosine monophosphate
- CDK:
-
Cyclin-dependent kinases
- CHOP:
-
C/EBP homologous protein
- ChREBP:
-
Carbohydrate response element binding protein
- CREB:
-
CAMP response element binding
- CREM:
-
CAMP response element modulator
- Clec4e:
-
C-type Lectin receptor 4e
- CYP8B1:
-
Cholesterol 12α -hydroxylase
- EndMT:
-
Endothelial-mesenchymal transition
- EC:
-
Endothelial cell
- HAEC:
-
Human aortic endothelial cells
- HBMECs:
-
Human brain microvascular endothelial cells
- HCAECs:
-
Human coronary artery endothelial cells
- HDL:
-
High-density lipoprotein
- HCD:
-
High-cholesterol diet
- Hif:
-
Hypoxia inducible factor
- HO-1:
-
Heme oxygenase-1
- HUVECs:
-
Human umbilical vein endothelial cells
- IL-6:
-
Interleukin-6
- Ire1:
-
Inositol-requiring transmembrane kinase/endonuclease 1
- IRF7:
-
IFN regulatory factor 7
- I/R:
-
Ischemia/Reperfusion
- JNK:
-
C-Jun N-terminal kinase
- LOX1R:
-
Lectin-like oxidized LDL receptor 1
- MMP:
-
Matrix metalloproteinase
- NO:
-
Nitric oxide
- NRF2:
-
Nuclear factor erythroid 2-related factor 2
- oxLDL:
-
Oxidized low-density lipoprotein
- PI3K/AKT:
-
Phosphatidylinositol-4,5-bisphosphate 3-kinase/ protein kinase B
- PLGF:
-
Placental growth factor
- rECs:
-
Rabbit endothelial cells
- Rock1/2:
-
Rho-associated, coiled-coil containing protein kinase 1 and 2
- Scd1:
-
Stearoyl-CoA desaturase 1
- SAPK:
-
Stress-activated protein kinase
- SMC:
-
Smooth muscle cell
- SR-B1:
-
Scavenger receptors B1
- SUMO:
-
Small Ubiquitin-like Modifier
- TNF-α:
-
Tumor necrosis factor-α
- TGF-β:
-
Transforming growth factor-β
- TGRL:
-
Triglyceride-rich lipoproteins
- TLR:
-
Toll-like receptor
- TL:
-
TGRL lipolysis products
- TDB:
-
D-( +)-trehalose 6,6'-dibehenate
- VSMCs:
-
Vascular smooth muscle cells
- VEGF:
-
Vascular endothelial growth factor
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This work was supported by grants from the Ningbo Natural Science Foundation of China (2019A610341).
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BYW and JQZ designed the manuscript. BYW wrote the manuscript. JQ, BYL, and XYS revised the manuscript. JFL and FY revised the tables. JHL and XY revised the figures. All authors approved the manuscript for publication.
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Wang, B., Yang, X., Sun, X. et al. ATF3 in atherosclerosis: a controversial transcription factor. J Mol Med 100, 1557–1568 (2022). https://doi.org/10.1007/s00109-022-02263-7
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DOI: https://doi.org/10.1007/s00109-022-02263-7