Atf3, or activating transcription factor 3, is a member of the ATF/CREB protein family. It acts as a transcription suppressor or activator, playing a vital role in the cellular adaptive-response network. Multiple extracellular signals, such as endoplasmic reticulum stress, cytokines, chemokines, and LPS, can induce its expression. Atf3 is involved in regulating various biological processes, including metabolism, immunity, and oncogenesis [4].

In abdominal aortic aneurysm (AAA), the deficiency of Atf3 in vascular smooth muscle cells promotes AAA formation in Ang II-induced AAA mice. PDGFRB was identified as its target, mediating vascular smooth muscle cell proliferation at the early stage of AAA, and Atf3 suppresses mitochondria-dependent apoptosis at the advanced stage by upregulating BCL2 [1].

In atherosclerosis, its role is controversial. In endothelial cells, overexpression aggravates oxidative stress and inflammation, while in macrophages and liver cells, it can act as a negative regulator of inflammation and promote cholesterol metabolism [2].

In metabolic dysfunction-associated steatohepatitis (MASH), Atf3 in macrophages regulates the glucose-fatty acid cycle, attenuating hepatocyte steatosis and fibrogenesis in hepatic stellate cells [3].

In conclusion, Atf3 is a key regulator in multiple biological processes and diseases. Gene knockout and conditional knockout mouse models have revealed its role in diseases like AAA, atherosclerosis, and MASH. Understanding Atf3's functions can potentially lead to new therapeutic strategies for these diseases.