PMID- 33096109
OWN - NLM
STAT- MEDLINE
DCOM- 20210111
LR  - 20211204
IS  - 1096-0333 (Electronic)
IS  - 0041-008X (Linking)
VI  - 409
DP  - 2020 Dec 15
TI  - Zafirlukast prevented ox-LDL-induced formation of foam cells.
PG  - 115295
LID - S0041-008X(20)30421-X [pii]
LID - 10.1016/j.taap.2020.115295 [doi]
AB  - Atherosclerosis (AS), a common arterial disease, is one of the main pathological 
      roots of cardiovascular disease. The formation and accumulation of foam cells is 
      an important event in early AS. An imbalance between cholesterol uptake and 
      efflux is the primary cause of foam cell formation. Although research has focused 
      on preventing the formation of foam cells, a safe and effective therapy has to be 
      found. Zafirlukast is a widely useful type 1 cysteinyl leukotriene receptor 
      (CysLT1R) antagonist with a good safety profile. Zafirlukast is the most used for 
      the treatment of asthma and allergic rhinitis. However, the effect of zafirlukast 
      on preventing the formation of foam cells has not been determined. The aim of 
      this study was to investigate whether zafirlukast prevented macrophages from 
      transforming into foam cells. Our data show that zafirlukast reduced the 
      expression of CD36 and lipoprotein receptor-1 (LOX-1), which are responsible for 
      lipid uptake. In addition, zafirlukast enhanced the activity of ATP-Binding 
      Cassette A1 (ABCA1) and ATP-binding cassette transporter G1 (ABCG1), leading to 
      the acceleration of cholesterol efflux. Furthermore, zafirlukast influenced the 
      activity of the phosphatidylinositol-3-kinase (PI3K)/Akt signaling pathway, which 
      mediates the expression of ABCA1 and ABCG1. In summary, our data indicate that 
      zafirlukast might be a potential treatment strategy for AS by mediating lipid 
      metabolism and preventing the formation of foam cells.
CI  - Copyright (c) 2020. Published by Elsevier Inc.
FAU - Song, Qiang
AU  - Song Q
AD  - Department of Structural Heart Disease, the First Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an 710061, Shanxi, China.
FAU - Hu, Zhi
AU  - Hu Z
AD  - Department of Structural Heart Disease, the First Affiliated Hospital of Xi'an 
      Jiaotong University, Xi'an 710061, Shanxi, China.
FAU - Xie, Xinming
AU  - Xie X
AD  - Department of Respiratory and Critical Care Medicine, the First Affiliated 
      Hospital of Xi'an Jiaotong University, Xi'an 710061, Shanxi, China.
FAU - Cai, Hui
AU  - Cai H
AD  - Department of vascular surgery, the First Affiliated Hospital of Xi'an Jiaotong 
      University, Xi'an 710061, Shanxi, China. Electronic address: caihui6081@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201020
PL  - United States
TA  - Toxicol Appl Pharmacol
JT  - Toxicology and applied pharmacology
JID - 0416575
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Indoles)
RN  - 0 (Lipoproteins, LDL)
RN  - 0 (Phenylcarbamates)
RN  - 0 (Sulfonamides)
RN  - 0 (Tosyl Compounds)
RN  - 0 (oxidized low density lipoprotein)
RN  - XZ629S5L50 (zafirlukast)
SB  - IM
MH  - ATP-Binding Cassette Transporters/metabolism
MH  - Animals
MH  - Atherosclerosis/drug therapy/metabolism
MH  - Biological Transport/drug effects
MH  - Cell Line
MH  - Foam Cells/*drug effects/metabolism
MH  - Indoles
MH  - Lipid Metabolism/drug effects
MH  - Lipoproteins, LDL/*metabolism
MH  - Macrophages/drug effects/metabolism
MH  - Mice
MH  - Phenylcarbamates
MH  - RAW 264.7 Cells
MH  - Signal Transduction/drug effects
MH  - Sulfonamides
MH  - Tosyl Compounds/*pharmacology
OTO - NOTNLM
OT  - ABCA1
OT  - ABCG1
OT  - Atherosclerosis
OT  - CD36
OT  - LOX-1
OT  - PI3K/AKT
OT  - Scavenger receptor
EDAT- 2020/10/24 06:00
MHDA- 2021/01/12 06:00
CRDT- 2020/10/23 20:10
PHST- 2020/03/22 00:00 [received]
PHST- 2020/07/15 00:00 [revised]
PHST- 2020/10/14 00:00 [accepted]
PHST- 2020/10/24 06:00 [pubmed]
PHST- 2021/01/12 06:00 [medline]
PHST- 2020/10/23 20:10 [entrez]
AID - S0041-008X(20)30421-X [pii]
AID - 10.1016/j.taap.2020.115295 [doi]
PST - ppublish
SO  - Toxicol Appl Pharmacol. 2020 Dec 15;409:115295. doi: 10.1016/j.taap.2020.115295. 
      Epub 2020 Oct 20.