Cigarette smoke extract induces foam cell formation by impairing machinery involved in lipid droplet degradation.
Atherosclerosis
Cigarette smoke
Foam cell
Lipid droplet
Lipophagy
Journal
Pflugers Archiv : European journal of physiology
ISSN: 1432-2013
Titre abrégé: Pflugers Arch
Pays: Germany
ID NLM: 0154720
Informations de publication
Date de publication:
01 Nov 2023
01 Nov 2023
Historique:
received:
05
07
2023
accepted:
24
10
2023
revised:
21
10
2023
medline:
1
11
2023
pubmed:
1
11
2023
entrez:
1
11
2023
Statut:
aheadofprint
Résumé
The formation of foam cells, lipid-loaded macrophages, is the hallmark event of atherosclerosis. Since cigarette smoking is a risk factor for developing atherosclerosis, the current study investigated the effects of cigarette smoke extract (CSE) on different events like expressions of genes involved in lipid influx and efflux, lipophagy, etc., that play vital roles in foam cell formation. The accumulation of lipids after CSE treatment U937 macrophage cells was examined by staining lipids with specific dyes: Oil red O and BODIPY493/503. Results showed an accumulation of lipids in CSE-treated cells, confirming foam cell formation by CSE treatment. To decipher the mechanism, the levels of CD36, an ox-LDL receptor, and ABCA1, an exporter of lipids, were examined in CSE-treated and -untreated U937 cells by real-time PCR and immunofluorescence analysis. Consistent with lipid accumulation, an increased level of CD36 and a reduction in ABCA1 were observed in CSE-treated cells. Moreover, CSE treatment caused inhibition of lipophagy-mediated lipid degradation by blocking lipid droplets (LDs)-lysosome fusion and increasing the lysosomal pH. CSE also impaired mitochondrial lipid oxidation. Thus, the present study demonstrates that CSE treatment affects lipid homeostasis by altering its influx and efflux, lysosomal degradation, and mitochondrial utilization, leading to the formation of lipid-loaded foam cells. Moreover, the current study also showed that the leucine supplement caused a significant reduction of CSE-induced foam cell formation in vitro. Thus, the current study provides insight into CS-induced atherosclerosis and an agent to combat the disease.
Identifiants
pubmed: 37910205
doi: 10.1007/s00424-023-02870-4
pii: 10.1007/s00424-023-02870-4
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Department of Biotechnology, Ministry of Science and Technology, India
ID : DBT/JRF/BET-16/I/2016/AL/51-458
Organisme : Department of Biotechnology, Ministry of Science and Technology, India
ID : BTPR5852/BRB/10/1105/2012
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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