Inflammatory corpuscle AIM2 facilitates macrophage foam cell formation by inhibiting cholesterol efflux protein ABCA1.
ATP Binding Cassette Transporter 1
/ metabolism
Foam Cells
/ metabolism
Humans
Cholesterol
/ metabolism
Lipoproteins, LDL
/ metabolism
DNA-Binding Proteins
/ metabolism
Atherosclerosis
/ metabolism
THP-1 Cells
Macrophages
/ metabolism
Computational Biology
/ methods
Apoptosis
Inflammation
/ metabolism
ABCA1
AIM2
Atherosclerosis
Cholesterol efflux
Inflammatory corpuscle
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
11 May 2024
11 May 2024
Historique:
received:
02
02
2024
accepted:
06
05
2024
medline:
12
5
2024
pubmed:
12
5
2024
entrez:
11
5
2024
Statut:
epublish
Résumé
The inflammatory corpuscle recombinant absents in melanoma 2 (AIM2) and cholesterol efflux protein ATP binding cassette transporter A1(ABCA1) have been reported to play opposing roles in atherosclerosis (AS) plaques. However, the relationship between AIM2 and ABCA1 remains unclear. In this study, we explored the potential connection between AIM2 and ABCA1 in the modulation of AS by bioinformatic analysis combined with in vitro experiments. The GEO database was used to obtain AS transcriptional profiling data; screen differentially expressed genes (DEGs) and construct a weighted gene co-expression network analysis (WGCNA) to obtain AS-related modules. Phorbol myristate acetate (PMA) was used to induce macrophage modelling in THP-1 cells, and ox-LDL was used to induce macrophage foam cell formation. The experiment was divided into Negative Control (NC) group, Model Control (MC) group, AIM2 overexpression + ox-LDL (OE AIM2 + ox-LDL) group, and AIM2 short hairpin RNA + ox-LDL (sh AIM2 + ox-LDL) group. The intracellular cholesterol efflux rate was detected by scintillation counting; high-performance liquid chromatography (HPLC) was used to detect intracellular cholesterol levels; apoptosis levels were detected by TUNEL kit; levels of inflammatory markers (IL-1β, IL-18, ROS, and GSH) were detected by ELISA kits; and levels of AIM2 and ABCA1 proteins were detected by Western blot. Bioinformatic analysis revealed that the turquoise module correlated most strongly with AS, and AIM2 and ABCA1 were co-expressed in the turquoise module with a trend towards negative correlation. In vitro experiments demonstrated that AIM2 inhibited macrophage cholesterol efflux, resulting in increased intracellular cholesterol levels and foam cell formation. Moreover, AIM2 had a synergistic effect with ox-LDL, exacerbating macrophage oxidative stress and inflammatory response. Silencing AIM2 ameliorated the above conditions. Furthermore, the protein expression levels of AIM2 and ABCA1 were consistent with the bioinformatic analysis, showing a negative correlation. AIM2 inhibits ABCA1 expression, causing abnormal cholesterol metabolism in macrophages and ultimately leading to foam cell formation. Inhibiting AIM2 may reverse this process. Overall, our study suggests that AIM2 is a reliable anti-inflammatory therapeutic target for AS. Inhibiting AIM2 expression may reduce foam cell formation and, consequently, inhibit the progression of AS plaques.
Identifiants
pubmed: 38734775
doi: 10.1038/s41598-024-61495-4
pii: 10.1038/s41598-024-61495-4
doi:
Substances chimiques
ATP Binding Cassette Transporter 1
0
Cholesterol
97C5T2UQ7J
ABCA1 protein, human
0
Lipoproteins, LDL
0
oxidized low density lipoprotein
0
AIM2 protein, human
0
DNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
10782Subventions
Organisme : 2020 Hainan Medical College Scientific Research Cultivation Fund Project
ID : HYPY202005
Organisme : The Second National Famous Traditional Chinese Medicine Inheritance Studio (Yang Hua Studio)
ID : [2022] No.245
Organisme : Natural Science Foundation of Hainan Province
ID : 822QN476
Informations de copyright
© 2024. The Author(s).
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