Ccn4, also known as WNT1-Inducible Signaling Pathway Protein 1 (WISP1), is a highly conserved, secreted cysteine-rich matricellular protein. It belongs to the CCN protein family and is a downstream target of β-catenin. Ccn4 plays diverse roles in various cellular mechanisms such as cell proliferation, migration, invasion, angiogenesis, wound healing, repair, and apoptosis. It is involved in multiple disease-related pathways, including those related to cancer, fibrosis, metabolic and inflammatory disorders [1,3,4,5,6]. Genetic models, like gene knockout mouse models, are valuable for studying its functions.

In a high-fat-fed ApoE-/-mouse model, Ccn4 deficiency led to increased apoptosis and atherosclerotic plaque burden in the brachiocephalic artery and aortic root, while Ccn4 overexpression had the opposite effect, reducing plaque burden, apoptosis, macrophage infiltration, and lipid core size [2]. In an aneurysm mouse model using ApoE-/-mice, deletion of Ccn4 significantly reduced aneurysm severity, including the number of ruptured aortae, aortic area, and aneurysm grade score. It also decreased macrophage infiltration and cell apoptosis, improving aortic integrity [7].

In conclusion, Ccn4 has essential functions in regulating cell apoptosis, migration, and proliferation, which are crucial in disease processes such as atherosclerosis and aneurysm formation. The use of Ccn4 knockout mouse models has significantly contributed to understanding its role in these specific disease areas, providing insights into potential therapeutic targets for these diseases.