ALDH2 deficiency inhibits Ox-LDL induced foam cell formation via suppressing CD36 expression
ALDH2 deficiency inhibits Ox-LDL induced foam cell formation via suppressing CD36 expression
复制标题
ALDH2 缺陷通过抑制 CD36 表达抑制 Ox-LDL 诱导的泡沫细胞形成
DOI：
10.1016/j.bbrc.2019.02.012
复制
发表时间：
2019-04-23
影响因子：
3.1
通讯作者：
Chen, Yuguo
中科院分区：
文献类型：
--
作者：
Wei, Shujian;Zhang, Luetao;Chen, Yuguo
泡沫细胞的形成在动脉粥样硬化的发生和发展中起着重要作用。醛脱氢酶2（ALDH 2）是醛代谢的关键酶，与冠状动脉疾病相关，并影响动脉粥样硬化斑块的脆弱性。然而，ALDH 2在泡沫细胞形成中的作用仍不清楚。使用来自ALDH 2缺陷小鼠和对照小鼠的腹腔巨噬细胞，我们发现ALDH 2缺陷抑制了由氧化低密度脂蛋白（ox-LDL）诱导的泡沫细胞形成，但不抑制乙酰化低密度脂蛋白（ac-LDL）体外诱导的泡沫细胞形成。与ox-LDL孵育后，ALDH 2缺陷型巨噬细胞表达的CD 36水平降低，但其他脂代谢相关蛋白包括SRA、LOX-1、ABCA-1、ABCG-1和ACAT-1在ALDH 2（-/-）巨噬细胞中的表达没有改变。使用CD 36抑制剂，我们证实了CD 36有助于ALDH 2对泡沫细胞形成的影响。在ox-LDL处理的ALDH 2（-/-）巨噬细胞中，PPAR γ下调。4-ALDH 2缺乏可使HNE增加，高浓度的4-HNE抑制了PPAR γ的表达。这些数据表明，ALDH 2通过4-HNE/PPAR γ/CD 36 u途径在泡沫细胞形成中起重要作用。(C)2019由Elsevier Inc.出版
Foam cell formation plays an important role in the initiation and progression of atherosclerosis. Aldehyde dehydrogenase 2 (ALDH2), a key enzyme for aldehyde metabolism, is associated with coronary artery disease and affects atherosclerotic plaque vulnerability. However, the role of ALDH2 in foam cell formation remains unclear. Using peritoneal macrophages from ALDH2-deficient and control mice, we found that ALDH2 deficiency suppressed foam cell formation induced by oxidized low-density lipoproteins (ox-LDL) but not acetylated low-density lipoproteins (ac-LDL) ex vivo. After incubation with ox-LDL, ALDH2-deficient macrophages expressed lower levels of CD36 but the expression of other lipid metabolism-related proteins including SRA, LOX-1, ABCA-1, ABCG-1 and ACAT-1 was not changed in ALDH2(-/-) macrophages. Using CD36 inhibitor, we confirmed that CD36 contributes to the effect of ALDH2 on foam cell formation. PPAR gamma was downregulated in ox-LDL treated ALDH2(-/-) macrophages. 4-HNE was increased by ALDH2 deficiency and high concentration of 4-HNE suppressed the expression of PPAR gamma. These data suggest that ALDH2 plays an important role in foam cell formation via 4-HNE/PPAR gamma/CD36 upathway. (C) 2019 Published by Elsevier Inc.