Fatty acid binding protein 3 deficiency limits atherosclerosis development via macrophage foam cell formation inhibition

Atherosclerosis is the underlying contributing factor of cardiovascular disease, which is a process of inflammation and lipid-rich lesion. Macrophage-derived foam cell is a key hallmark of atherosclerosis and connected with various factors of lipid metabolism. Here, we showed that fatty acid binding protein 3 (FABP3) was upregulated in the aorta of ApoE(-/)(-) mice with high-fat-diet (HFD) feeding. Knockdown of FABP3 in HFD-fed ApoE(-/)(-) mice notably facilitated cholesterol efflux, inhibited macrophage foam cell formation, and thus prevented atherogenesis. Furthermore, FABP3 silencing decreased the expression of peroxisome proliferator-activated receptor gamma (PPAR gamma). Mechanistic studies had disclosed the involvement of PPAR gamma signaling in balancing cholesterol uptake and efflux and diminishing foam cell formation. These findings firstly revealed an anti-atherogenic role of FABP3 silencing in preventing foamy macrophage formation partly through PPAR gamma, which might be a beneficial approach for therapying atherosclerosis.