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
|
Resource |
Mice |
RBRC05808 |