1. The senescent marker p16INK4a enhances macrophage foam cells formation.
- Author
-
Siew WS, Tang YQ, Goh BH, and Yap WH
- Subjects
- Humans, THP-1 Cells, Macrophages metabolism, Cholesterol metabolism, Biomarkers metabolism, Scavenger Receptors, Class E metabolism, Scavenger Receptors, Class E genetics, Foam Cells metabolism, Cellular Senescence genetics, Cyclin-Dependent Kinase Inhibitor p16 metabolism, Cyclin-Dependent Kinase Inhibitor p16 genetics, Autophagy genetics, CD36 Antigens metabolism, CD36 Antigens genetics, Lipoproteins, LDL metabolism
- Abstract
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: 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: 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: This study provides insights on p16INK4a in mediating macrophages foam cells formation, cellular senescence, and foam cells formation., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)
- Published
- 2024
- Full Text
- View/download PDF