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

Shujian Wei; Luetao Zhang; Bailu Wang; Yu Zhao; Qianqian Dong; Chang Pan; Chuanbao Li; Dayu He; Qiuhuan Yuan; Feng Xu; Yuguo Chen

doi:10.1016/j.bbrc.2019.02.012

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

Biochem Biophys Res Commun. 2019 Apr 23;512(1):41-48. doi: 10.1016/j.bbrc.2019.02.012. Epub 2019 Mar 8.

Authors

Shujian Wei¹, Luetao Zhang¹, Bailu Wang², Yu Zhao¹, Qianqian Dong¹, Chang Pan¹, Chuanbao Li¹, Dayu He¹, Qiuhuan Yuan³, Feng Xu⁴, Yuguo Chen⁵

Affiliations

¹ 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.
² Clinical Trial Center, Qilu Hospital, Shandong University, Jinan, China.
³ 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.
⁴ 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. Electronic address: xufengsdu@126.com.
⁵ 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. Electronic address: chen919085@sdu.edu.cn.

PMID: 30853183
DOI: 10.1016/j.bbrc.2019.02.012

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.

Keywords: Aldehyde dehydrogenase 2; Atherosclerosis; CD36; Foam cell; PPARγ.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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