Macrophage Gpx4 deficiency aggravates foam cell formation by regulating the expression of scavenger receptors, ABCA1, and ABCG1
Macrophage Gpx4 deficiency aggravates foam cell formation by regulating the expression of scavenger receptors, ABCA1, and ABCG1
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DOI：
10.1002/cbin.12057
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发表时间：
2023-06-12
影响因子：
3.9
通讯作者：
Dai，Xiaoyan
中科院分区：
文献类型：
--
作者：
Zhou，Jingquan;Wu，Suhua;Dai，Xiaoyan
Macrophage‐derived foam cell formation is critical for the initiation and development of atherosclerosis, which contributes to atherosclerotic cardiovascular disease (ASCVD). Glutathione peroxidase 4 (GPX4), a crucial ferroptosis regulator, protects cells from excessive oxidative stress by neutralizing lipid peroxidation. However, the role of macrophage GPX4 in foam cell formation remains unknown. We reported that oxidized low‐density lipoprotein (oxLDL) upregulated GPX4 expression in macrophages. Using the Cre‐loxP system, we generated myeloid cell‐specificGpx4knockout (Gpx4myel‐KO) mice. Bone marrow‐derived macrophages (BMDMs) were isolated from WT andGpx4myel‐KOmice and incubated with modified low‐density lipoprotein (LDL). We found thatGpx4deficiency promoted foam cell formation and increased the internalization of modified LDL. Mechanistic studies unveiled thatGpx4knockout upregulated scavenger receptor type A and LOX‐1 expression and downregulated ABCA1 and ABCG1 expression. Collectively, our study lends a novel insight into the role of GPX4 in suppressing macrophage‐derived foam cell formation and suggests GPX4 as a promising therapeutic target to interfere with atherosclerosis‐related diseases.
