Department of Cardiology, The Central Hospital Affiliated to Shenyang Medical College, Shenyang, Liaoning, People's Republic of China; Department of Cardiology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang, Liaoning, People's Republic of China.
Department of Cardiology, The Second Affiliated Hospital of Shenyang Medical College, Shenyang, Liaoning, People's Republic of China.
Exp Cell Res. 2021 Oct 1;407(1):112768. doi: 10.1016/j.yexcr.2021.112768. Epub 2021 Aug 8.
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致病因素，它是一个炎症和富含脂质的病变过程。巨噬细胞源性泡沫细胞是动脉粥样硬化的一个关键标志，与脂质代谢的各种因素有关。在这里，我们发现载脂蛋白 E 基因敲除小鼠在高脂饮食喂养下脂肪酸结合蛋白 3（FABP3）在主动脉中上调。在高脂饮食喂养的 ApoE 小鼠中敲低 FABP3 可明显促进胆固醇流出，抑制巨噬细胞泡沫细胞形成，从而防止动脉粥样硬化形成。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。机制研究表明，PPARγ 信号参与平衡胆固醇摄取和流出，减少泡沫细胞形成。这些发现首次揭示了 FABP3 沉默通过 PPARγ 抑制泡沫巨噬细胞形成的抗动脉粥样硬化作用，这可能是治疗动脉粥样硬化的一种有益方法。
