RRC ID 54515
Author Wei S, Zhang L, Bailu Wang, Zhao Y, Dong Q, Pan C, Li C, He D, Yuan Q, Xu F, Chen Y.
Title ALDH2 deficiency inhibits Ox-LDL induced foam cell formation via suppressing CD36 expression.
Journal Biochem Biophys Res Commun
Abstract 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.
Volume 512(1)
Pages 41-48
Published 2019-4-23
DOI 10.1016/j.bbrc.2019.02.012
PII S0006-291X(19)30193-7
PMID 30853183
MeSH Aldehyde Dehydrogenase, Mitochondrial / deficiency* Aldehyde Dehydrogenase, Mitochondrial / genetics Aldehydes / metabolism Aldehydes / pharmacology Animals Apoptosis / drug effects Atherosclerosis / etiology Atherosclerosis / metabolism Atherosclerosis / pathology CD36 Antigens / metabolism* Down-Regulation Foam Cells / drug effects Foam Cells / metabolism* Foam Cells / pathology In Vitro Techniques Lipoproteins, LDL / metabolism* Lipoproteins, LDL / pharmacology Macrophages, Peritoneal / drug effects Macrophages, Peritoneal / metabolism Macrophages, Peritoneal / pathology Male Mice Mice, Inbred C57BL Mice, Knockout Models, Cardiovascular PPAR gamma / metabolism Signal Transduction
IF 2.705
Times Cited 2
Mice RBRC05808