Macrophage lipid metabolism is transcriptionally regulated by peroxisome proliferator-activated receptor gamma (PPARγ), and its target gene fatty acid binding protein 4 (FABP4) accelerates the progression of atherosclerosis in mouse models.
Many of the up-regulated genes-including the hyaluron receptor CD44, vasoconstrictor endothelin-1, smooth muscle growth factor heparin-binding EGF-like growth factor, and fatty acid binding protein-4-had been previously described as linked to the development of atherosclerosis and other chronic inflammatory diseases.
Our findings indicate the involvement of FABP4 and leptin in the progression of atherosclerosis and plaque rupture, and suggest that down-regulation of PPAR/adipocytokine signaling within plaques may have therapeutic potential.
Previous studies have shown that reduced levels of the adipocyte fatty acid binding protein (FABP)4 (AFABP/aP2), result in metabolic improvement including potentiated insulin sensitivity and attenuated atherosclerosis.
Recent studies have demonstrated that FABP4 regulates metabolic and inflammatory pathways, and in mouse models its inhibition can improve type 2 diabetes mellitus and atherosclerosis.
Recent work has demonstrated that macrophage FABP4 integrates inflammatory and lipid metabolic responses, thereby contributing to the development of insulin resistance and atherosclerosis.
These data suggest that FABP4 plays a key role in Hcy-mediated disturbance of lipid metabolism and that DNMT1 may be a novel therapeutic target in Hcy-related atherosclerosis.
To reveal a correlation between periodontitis and systemic diseases as well as a relevant molecular pathway, we investigated the effects of <i>Porphyromonas gingivalis</i> and <i>Fusobacterium nucleatum</i>, which play roles in chronic periodontitis progression, on Raw264.7 and THP-1 macrophages.Infection with <i>P. gingivalis</i> or <i>F. nucleatum</i> significantly induced the expression of fatty acid binding protein 4 (FABP4), one of the most important adipokines that play a role in the progression of systemic diseases such as atherosclerosis and type 2 diabetes.