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

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.

• Authors: Shujian Wei, Luetao Zhang, Bailu Wang, Yu Zhao, Qianqian Dong, Chang Pan, Chuanbao Li, Dayu He, Qiuhuan Yuan, Feng Xu, Yuguo Chen
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 512 Issue 1 Pg. 41-48 (04 23 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 30853183 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019. Published by Elsevier Inc.

Chemical References

• Aldehydes
• CD36 Antigens
• Cd36 protein, mouse
• Lipoproteins, LDL
• PPAR gamma
• oxidized low density lipoprotein
• ALDH2 protein, mouse
• Aldehyde Dehydrogenase, Mitochondrial
• 4-hydroxy-2-nonenal

Topics

• Aldehyde Dehydrogenase, Mitochondrial (deficiency, genetics)
• Aldehydes (metabolism, pharmacology)
• Animals
• Apoptosis (drug effects)
• Atherosclerosis (etiology, metabolism, pathology)
• CD36 Antigens (metabolism)
• Down-Regulation
• Foam Cells (drug effects, metabolism, pathology)
• In Vitro Techniques
• Lipoproteins, LDL (metabolism, pharmacology)
• Macrophages, Peritoneal (drug effects, metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Models, Cardiovascular
• PPAR gamma (metabolism)
• Signal Transduction