Highlights
- •SAA and IL-1β increase the expression of cavin-1 and caveolin-1 via activation of NF-κB.
- •SAA and IL-1β promote LDL transcytosis across endothelial cells.
- •SAA and IL-1β accelerate the formation of atherosclerotic lesions.
Abstract
Background and aims
Inflammatory molecules play important roles in atherosclerosis. We aimed to illustrate
the roles of serum amyloid A (SAA), and interleukin (IL)-1β in low density lipoproteins
(LDL) transcytosis and atherosclerosis.
Methods
Effects of SAA and IL-1β on transcytosis of LDL were measured by an in vitro LDL transcytosis model. NF-κB/caveolin-1/cavin-1 pathway activation was investigated
by Western blots and ELISA. Effects of SAA and IL-1β on the retention of LDL in aorta
of C57BL/6J mice were detected by IVIS spectrum. Effects of SAA and IL-1β on atherosclerosis
in Apoe−/− mice were examined by Oil Red O staining.
Results
SAA and IL-1β stimulated LDL transcytosis across endothelial cells (ECs), which was
accompanied by an increase in LDL uptake by ECs. SAA and IL-1β enhanced the activity
of nuclear factor (NF)-κB, consequently facilitating an up-regulation of proteins
involved in caveolae formation, including caveolin-1 and cavin-1, along with an assembly
of NLRP3 inflammasome. Furthermore, SAA- and IL-1β-induced effects were blocked by
NF-κB subunit p65 siRNA. Meanwhile, SAA- and IL-1β-induced LDL transcytosis were effectively
blocked by caveolin-1 siRNA or cavin-1 siRNA. Interestingly, SAA and IL-1β facilitated
LDL entering into the aorta of C57BL/6J mice. In Apoe−/− mice, SAA and IL-1β increased the areas of lipid-rich atherosclerotic lesions in
the both ascending and root of aorta. Furthermore, a significant increase in the NLRP3
inflammasome, accompanied by accumulation of cavin-1 and caveolin-1, was observed
in the aortic endothelium of Apoe −/− mice.
Conclusions
SAA and IL-1β accelerated LDL transcytosis via the NF-κB/caveolin-1/cavin-1 axis.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: March 11, 2023
Accepted:
March 8,
2023
Received in revised form:
March 6,
2023
Received:
July 11,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier B.V. All rights reserved.
