ALDH2 deficiency inhibits Ox-LDL induced foam cell formation via suppressing CD36 expression

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 ce...

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Veröffentlicht in:Biochemical and biophysical research communications 2019-04, Vol.512 (1), p.41-48
Hauptverfasser: Wei, Shujian, Zhang, Luetao, Bailu wang, Zhao, Yu, Dong, Qianqian, Pan, Chang, Li, Chuanbao, He, Dayu, Yuan, Qiuhuan, Xu, Feng, Chen, Yuguo
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Sprache:eng
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Zusammenfassung: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. •Aldh2 deficiency reduces ox-LDL rather than ac-LDL induced macrophage derived foam cell formation.•CD36 contributes to the decreased foam cell formation in ox-LDL treated ALDH2 deficient macrophages.•ALDH2 deficiency increases the level of 4-HNE and downregulates the expression of PPARγ in ox-LDL treated macrophages.•ALDH2 deficiency induced more cell apoptosis via promoting phosphorylation of P38 MAPK and suppressing phosphorylation of AKT.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2019.02.012