Department of Emergency, Qilu Hospital, Shandong University, Jinan, China; Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China; Institute of Emergency and Critical Care Medicine, Shandong University, Jinan, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China; Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
Clinical Trial Center, Qilu Hospital, Shandong University, Jinan, China.
Biochem Biophys Res Commun. 2019 Apr 23;512(1):41-48. doi: 10.1016/j.bbrc.2019.02.012. Epub 2019 Mar 8.
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. PPARγ 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 PPARγ. These data suggest that ALDH2 plays an important role in foam cell formation via 4-HNE/PPARγ/CD36 pathway.
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（ALDH2）是一种关键的醛代谢酶，与冠状动脉疾病有关，并影响动脉粥样硬化斑块的脆弱性。然而，ALDH2 在泡沫细胞形成中的作用尚不清楚。使用 ALDH2 缺陷型和对照组小鼠的腹腔巨噬细胞，我们发现 ALDH2 缺陷抑制了氧化型低密度脂蛋白（ox-LDL）诱导的泡沫细胞形成，但对乙酰化低密度脂蛋白（ac-LDL）没有影响。在与 ox-LDL 孵育后，ALDH2 缺陷型巨噬细胞表达较低水平的 CD36，但 ALDH2 巨噬细胞中其他脂质代谢相关蛋白，包括 SRA、LOX-1、ABCA-1、ABCG-1 和 ACAT-1 的表达没有改变。使用 CD36 抑制剂，我们证实 CD36 有助于 ALDH2 对泡沫细胞形成的影响。在 ox-LDL 处理的 ALDH2 巨噬细胞中，PPARγ 下调。ALDH2 缺乏会增加 4-HNE，而高浓度的 4-HNE 会抑制 PPARγ 的表达。这些数据表明，ALDH2 通过 4-HNE/PPARγ/CD36 通路在泡沫细胞形成中发挥重要作用。
