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 γ (PPARγ). Mechanistic studies had disclosed the involvement of PPARγ 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 PPARγ, which might be a beneficial approach for therapying atherosclerosis.

动脉粥样硬化是心血管疾病的潜在促成因素，心血管疾病是炎症和富含脂质的病变的过程。巨噬细胞来源的泡沫细胞是动脉粥样硬化的关键标志，与脂质代谢的各种因素有关。在这里，我们发现脂肪酸结合蛋白 3 (FABP3) 在高脂肪饮食 (HFD) 喂养的 ApoE ^-/-小鼠的主动脉中上调。在 HFD 喂养的 ApoE 中敲除 FABP3 ^-/-小鼠显着促进胆固醇流出，抑制巨噬细胞泡沫细胞形成，从而防止动脉粥样硬化。此外，FABP3 沉默降低了过氧化物酶体增殖物激活受体γ（PPARγ）的表达。机制研究揭示了 PPARγ 信号参与平衡胆固醇摄取和流出以及减少泡沫细胞形成。这些发现首先揭示了 FABP3 沉默在部分通过 PPARγ 阻止泡沫巨噬细胞形成方面的抗动脉粥样硬化作用，这可能是治疗动脉粥样硬化的有益方法。