The senescent marker p16INK4a enhances macrophage foam cells formation.
Humans
Foam Cells
/ metabolism
Cellular Senescence
/ genetics
Cyclin-Dependent Kinase Inhibitor p16
/ metabolism
Autophagy
/ genetics
THP-1 Cells
CD36 Antigens
/ metabolism
Lipoproteins, LDL
/ metabolism
Macrophages
/ metabolism
Cholesterol
/ metabolism
Biomarkers
/ metabolism
Scavenger Receptors, Class E
/ metabolism
Autophagy
Cellular Senescence
Macrophage foam cell
p16INK4a
Journal
Molecular biology reports
ISSN: 1573-4978
Titre abrégé: Mol Biol Rep
Pays: Netherlands
ID NLM: 0403234
Informations de publication
Date de publication:
27 Sep 2024
27 Sep 2024
Historique:
received:
24
07
2024
accepted:
16
09
2024
medline:
27
9
2024
pubmed:
27
9
2024
entrez:
27
9
2024
Statut:
epublish
Résumé
The senescence marker p16INK4a, which constitutes part of the genome 9p21.3 cardiovascular disease (CVD) risk allele, is believed to play a role in foam cells formation. This study aims to unravel the role of p16INK4a in mediating macrophage foam cells formation, cellular senescence, and autophagy lysosomal functions. The mammalian expression plasmid pCMV-p16INK4a was used to induce p16INK4a overexpression in THP-1 macrophages. Next, wild-type and p16INK4a-overexpressed macrophages were incubated with oxidized LDL to induce foam cells formation. Lipids accumulation was evaluated using Oil-red-O staining and cholesterol efflux assay, as well as expression of scavenger receptors CD36 and LOX-1. Cellular senescence in macrophage foam cells were determined through analysis of senescence-associated β-galactosidase activity and other SASP factors expression. Meanwhile, autophagy induction was assessed through detection of autophagosome formation and LC3B/p62 markers expression. The findings showed that p16INK4a enhanced foam cells formation with increased scavenger receptors CD36 and LOX-1 expression and reduced cholesterol efflux in THP-1 macrophages. Besides, β-galactosidase activity was enhanced, and SASP factors such as IL-1α, TNF-α, and MMP9 were up-regulated. In addition, p16INK4a is also shown to induce autophagy, as well as increasing autophagy markers LC3B and p62 expression. This study provides insights on p16INK4a in mediating macrophages foam cells formation, cellular senescence, and foam cells formation.
Sections du résumé
BACKGROUND
BACKGROUND
The senescence marker p16INK4a, which constitutes part of the genome 9p21.3 cardiovascular disease (CVD) risk allele, is believed to play a role in foam cells formation. This study aims to unravel the role of p16INK4a in mediating macrophage foam cells formation, cellular senescence, and autophagy lysosomal functions.
METHODS
METHODS
The mammalian expression plasmid pCMV-p16INK4a was used to induce p16INK4a overexpression in THP-1 macrophages. Next, wild-type and p16INK4a-overexpressed macrophages were incubated with oxidized LDL to induce foam cells formation. Lipids accumulation was evaluated using Oil-red-O staining and cholesterol efflux assay, as well as expression of scavenger receptors CD36 and LOX-1. Cellular senescence in macrophage foam cells were determined through analysis of senescence-associated β-galactosidase activity and other SASP factors expression. Meanwhile, autophagy induction was assessed through detection of autophagosome formation and LC3B/p62 markers expression.
RESULTS
RESULTS
The findings showed that p16INK4a enhanced foam cells formation with increased scavenger receptors CD36 and LOX-1 expression and reduced cholesterol efflux in THP-1 macrophages. Besides, β-galactosidase activity was enhanced, and SASP factors such as IL-1α, TNF-α, and MMP9 were up-regulated. In addition, p16INK4a is also shown to induce autophagy, as well as increasing autophagy markers LC3B and p62 expression.
CONCLUSIONS
CONCLUSIONS
This study provides insights on p16INK4a in mediating macrophages foam cells formation, cellular senescence, and foam cells formation.
Identifiants
pubmed: 39331194
doi: 10.1007/s11033-024-09946-z
pii: 10.1007/s11033-024-09946-z
doi:
Substances chimiques
Cyclin-Dependent Kinase Inhibitor p16
0
oxidized low density lipoprotein
0
CD36 Antigens
0
Lipoproteins, LDL
0
CDKN2A protein, human
0
Cholesterol
97C5T2UQ7J
Biomarkers
0
Scavenger Receptors, Class E
0
CD36 protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1021Subventions
Organisme : Malaysian Ministry of Higher Education
ID : FRGS/1/2019/SKK08/TAYLOR/02/2
Organisme : Malaysian Ministry of Higher Education
ID : FRGS/1/2019/SKK08/TAYLOR/02/2
Organisme : Malaysian Ministry of Higher Education
ID : FRGS/1/2019/SKK08/TAYLOR/02/2
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature B.V.
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