Pim-2 kinase inhibits inflammation by suppressing the mTORC1 pathway in atherosclerosis.
Animals
Apolipoproteins E
/ deficiency
Atherosclerosis
/ blood
Diet, High-Fat
/ adverse effects
Inflammation
Lipid Metabolism
/ genetics
Lipoproteins, LDL
Macrophages
/ metabolism
Mechanistic Target of Rapamycin Complex 1
/ metabolism
Mice
Mice, Knockout
Protein Serine-Threonine Kinases
Proto-Oncogene Proteins
Signal Transduction
Tumor Necrosis Factor-alpha
/ blood
Up-Regulation
/ immunology
Pim-2
atherosclerosis
inflammatory
mTORC1
Journal
Aging
ISSN: 1945-4589
Titre abrégé: Aging (Albany NY)
Pays: United States
ID NLM: 101508617
Informations de publication
Date de publication:
21 09 2021
21 09 2021
Historique:
received:
01
07
2021
accepted:
07
09
2021
pubmed:
22
9
2021
medline:
2
2
2022
entrez:
21
9
2021
Statut:
ppublish
Résumé
Inflammatory immunity theory has raised considerable concern in the pathogenesis of atherosclerosis. Proviral integration site of murine 2 (Pim-2) kinases functions in apoptosis pathways and the anti-inflammatory response. Here, we investigated whether Pim-2 kinase inhibits atherosclerotic inflammation by suppressing the mTORC1 pathway. An atherosclerosis animal model was established by feeding ApoE The protein expression of Pim-2 was upregulated in ox-LDL-treated THP-1-derived macrophages and an atherosclerotic mouse model. Additionally, ox-LDL upregulated the protein expression of p-mTOR, p-S6K1 and p-4EBP1, intracellular lipid droplets, free cholesterol and cholesterylester and the mRNA expression of inflammatory cytokines, including IL-6, MCP-1, TLR-4 and TNF-α, in THP-1-derived macrophages. Functionally, overexpressed Pim-2 (Pim-2 OE) attenuated atherosclerotic inflammation associated with the mTORC1 signaling pathway These results indicated that Pim-2 kinase inhibits atherosclerotic inflammation by suppressing the mTORC1 pathway.
Sections du résumé
BACKGROUND
Inflammatory immunity theory has raised considerable concern in the pathogenesis of atherosclerosis. Proviral integration site of murine 2 (Pim-2) kinases functions in apoptosis pathways and the anti-inflammatory response. Here, we investigated whether Pim-2 kinase inhibits atherosclerotic inflammation by suppressing the mTORC1 pathway.
METHODS
An atherosclerosis animal model was established by feeding ApoE
RESULT
The protein expression of Pim-2 was upregulated in ox-LDL-treated THP-1-derived macrophages and an atherosclerotic mouse model. Additionally, ox-LDL upregulated the protein expression of p-mTOR, p-S6K1 and p-4EBP1, intracellular lipid droplets, free cholesterol and cholesterylester and the mRNA expression of inflammatory cytokines, including IL-6, MCP-1, TLR-4 and TNF-α, in THP-1-derived macrophages. Functionally, overexpressed Pim-2 (Pim-2 OE) attenuated atherosclerotic inflammation associated with the mTORC1 signaling pathway
CONCLUSIONS
These results indicated that Pim-2 kinase inhibits atherosclerotic inflammation by suppressing the mTORC1 pathway.
Identifiants
pubmed: 34547720
pii: 203547
doi: 10.18632/aging.203547
pmc: PMC8507271
doi:
Substances chimiques
Apolipoproteins E
0
Lipoproteins, LDL
0
Pim2 protein, mouse
0
Proto-Oncogene Proteins
0
Tumor Necrosis Factor-alpha
0
oxidized low density lipoprotein
0
Mechanistic Target of Rapamycin Complex 1
EC 2.7.11.1
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
22412-22431Références
Clin Sci (Lond). 2018 Jun 21;132(12):1243-1252
pubmed: 29930142
JACC Cardiovasc Interv. 2017 Sep 25;10(18):1832-1838
pubmed: 28935075
Atherosclerosis. 2018 Sep;276:98-108
pubmed: 30055326
Circ Res. 2014 May 9;114(10):1576-84
pubmed: 24687132
Cell Res. 2007 Aug;17(8):666-81
pubmed: 17680028
Environ Toxicol Pharmacol. 2016 Dec;48:94-102
pubmed: 27770661
J Biomed Sci. 2017 Feb 7;24(1):12
pubmed: 28173800
Immunology. 2010 Oct;131(2):174-82
pubmed: 20465571
Arch Cardiovasc Dis. 2016 Dec;109(12):708-715
pubmed: 27595467
J Cardiol. 2019 Jan;73(1):22-27
pubmed: 29907363
Circ Cardiovasc Interv. 2019 Jun;12(6):e007283
pubmed: 31177821
Biochem Biophys Res Commun. 2016 Sep 30;478(4):1528-33
pubmed: 27569284
Nat Rev Cardiol. 2019 Jul;16(7):389-406
pubmed: 30846875
Biomolecules. 2018 Aug 23;8(3):
pubmed: 30142970
Apoptosis. 2016 Nov;21(11):1203-1213
pubmed: 27651368
Int J Cardiol. 2013 Oct 15;168(6):5450-3
pubmed: 23972959
Sci Rep. 2016 Nov 30;6:38079
pubmed: 27901106
Cell. 2012 Apr 13;149(2):274-93
pubmed: 22500797
Acta Biochim Biophys Sin (Shanghai). 2011 Dec;43(12):940-7
pubmed: 22015781
Transplantation. 2018 Feb;102(2S Suppl 1):S44-S46
pubmed: 28230638
Mol Med Rep. 2017 Nov;16(5):7504-7512
pubmed: 28944837
Biomed Res Int. 2015;2015:240210
pubmed: 26064888
Can J Cardiol. 2012 Nov-Dec;28(6):631-41
pubmed: 22985787
Circ Res. 2014 Jan 31;114(3):549-64
pubmed: 24481845
Pharmacol Res. 2020 Feb;152:104626
pubmed: 31904507
Br J Clin Pharmacol. 2016 Nov;82(5):1267-1279
pubmed: 26551391
Am J Physiol Lung Cell Mol Physiol. 2015 Dec 1;309(11):L1344-53
pubmed: 26453516
J Mol Cell Cardiol. 2011 Aug;51(2):207-14
pubmed: 21600215
Nat Commun. 2019 Apr 17;10(1):1801
pubmed: 30996248
Cytokine. 2015 Oct;75(2):365-72
pubmed: 26142823
Am J Physiol Lung Cell Mol Physiol. 2014 Aug 1;307(3):L240-51
pubmed: 24816488
N Engl J Med. 1999 Jan 14;340(2):115-26
pubmed: 9887164
Circulation. 2019 Mar 5;139(10):e56-e528
pubmed: 30700139
Immunobiology. 2017 Feb;222(2):261-271
pubmed: 27692982
Int J Biochem Cell Biol. 2017 Dec;93:74-85
pubmed: 29108877
J Mol Cell Cardiol. 2014 Jan;66:72-82
pubmed: 24239845
Blood. 2013 Aug 29;122(9):1610-20
pubmed: 23818547
J Cardiovasc Pharmacol. 2019 Nov;74(5):379-388
pubmed: 31730559
Physiol Genomics. 2003 Sep 29;15(1):65-74
pubmed: 12902549
Exp Ther Med. 2019 Dec;18(6):4427-4435
pubmed: 31777546
Science. 2012 Mar 30;335(6076):1638-43
pubmed: 22461615
Circ Res. 2019 Jan 18;124(2):315-327
pubmed: 30653442
Science. 2005 Feb 18;307(5712):1098-101
pubmed: 15718470