Angptl4, also known as angiopoietin-like 4, is a secreted glycoprotein with a crucial role in lipid metabolism. It is predominantly expressed in adipose tissue and liver [2]. Angptl4 inhibits the activity of lipoprotein lipase (LPL), which hydrolyzes fatty acids from triglyceride-rich lipoproteins, thus promoting an increase in circulating triglyceride levels [2,3,7]. It is also involved in pathways related to metabolism, vascular homeostasis, angiogenesis, and is associated with metabolic and cardiovascular diseases [1,2,6,8]. Genetic models, such as KO/CKO mouse models, are valuable for studying its functions.

In atherosclerotic Apoe-/-mice, injection of ANGPTL4 protein reduced atherosclerotic plaque size, vascular inflammation, and led to a thicker fibrous cap, indicating more stable plaques. ANGPTL4 also modulated the phenotypic transition of vascular smooth muscle cells (SMCs) by down-regulating Krüppel-like factor 4 (KLF4), which is a modulator of the SMC phenotype [4]. In diabetic kidney disease, ANGPTL4 mutant mice showed a protective effect against fibrosis compared to control mice. Diabetes-induced fibrogenic phenotypes were accelerated in control mice but not in ANGPTL4 mutants, associated with reduced inflammation and mitochondrial damage [5].

In conclusion, Angptl4 is a multifunctional protein with essential roles in lipid metabolism, vascular stability, and inflammation-related processes. Findings from mouse models, like those in atherosclerosis and diabetic kidney disease, have revealed its significance in these disease areas, highlighting its potential as a therapeutic target for metabolic and cardiovascular diseases [1,2,4,5].