SIRT1 inhibits monocyte adhesion to the vascular endothelium by suppressing Mac-1 expression on monocytes

Autor: Chi Dae Kim, Seung Jin Lee, Min A. Jang, Seung Eun Baek
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
endocrine system diseases
THP-1 Cells
Transcriptional regulatory elements
Clinical Biochemistry
lcsh:Medicine
Biochemistry
Monocytes
0302 clinical medicine
Sirtuin 1
THP1 cell line
lcsh:QD415-436
Lipid signalling
biology
Chemistry
NF-kappa B
Chronic inflammation
Adhesion
Flow Cytometry
CREB-Binding Protein
Immunohistochemistry
Cell biology
Mechanisms of disease
medicine.anatomical_structure
030220 oncology & carcinogenesis
Molecular Medicine
lipids (amino acids
peptides
and proteins)
biological phenomena
cell phenomena
and immunity
Signal transduction
hormones
hormone substitutes
and hormone antagonists
Chromatin Immunoprecipitation
Endothelium
Transgene
Blotting
Western
CREB
Peripheral blood mononuclear cell
Article
lcsh:Biochemistry
03 medical and health sciences
Human Umbilical Vein Endothelial Cells
medicine
Humans
Molecular Biology
lcsh:R
Atherosclerosis
Toll-Like Receptor 2
enzymes and coenzymes (carbohydrates)
TLR2
030104 developmental biology
Mutagenesis
Site-Directed
biology.protein
Endothelium
Vascular
Zdroj: Experimental and Molecular Medicine, Vol 51, Iss 4, Pp 1-12 (2019)
Experimental & Molecular Medicine
ISSN: 2092-6413
1226-3613
Popis: SIRT1 signaling pathways modulate vascular inflammation; however, the precise role of SIRT1 in monocyte adhesion to the vascular endothelium, a key event initiating vascular inflammation, is unclear. Thus, this study investigated the roles and molecular interaction of SIRT1 and TLR2 in regulating monocyte adhesion to the vascular endothelium. In vitro, both Mac-1 expression and the endothelial adhesion of THP-1 cells stimulated with Pam3CSK4, a TLR2 ligand, were markedly increased in association with a decreased expression of SIRT1. In THP-1 cells stimulated with Pam3CSK4, the promoter activity and expression of SIRT1 were decreased. The TLR2-dependent suppression of SIRT1 expression in THP-1 cells was mediated by the transcription factors NF-κB and CREB, suggesting that the TLR2-mediated NF-κB and CREB signaling downregulated SIRT1 expression in monocytes. In peripheral blood monocytes (PBMCs) isolated from SIRT1 transgenic (TG) mice and THP-1 cells treated with recombinant SIRT1, both the increased Mac-1 expression and endothelial adhesion induced by Pam3CSK4 were significantly attenuated. In addition, the en face immunohistochemical study showed a marked increase in monocyte adhesion to the aortic endothelium of WT mice treated with Pam3CSK4, which was significantly attenuated in Pam3CSK4-treated SIRT1 TG mice. Moreover, a greater number of atherosclerotic plaques formed in WT mice fed a high-fat diet than in SIRT1 TG mice, indicating a pivotal role for SIRT1 in preventing vascular inflammation. Based on these results, SIRT1 might be a potential target for researchers aiming to develop therapeutic interventions for vascular inflammation, including atherosclerosis.
Atherosclerosis: Intervening in the early stages of plaque formation Researchers have identified a possible new tool, the signaling molecule SIRT1, to fight vascular diseases such as atherosclerosis, hardening of the arteries. In atherosclerosis, plaque builds up in arteries, restricting blood flow and potentially causing heart attack or stroke. Early in the disease, white blood cells called monocytes stick to artery walls, triggering inflammation. Administering SIRT1 was known to decrease inflammation, but how it did so was unclear. Chi Dae Kim at Pusan National University in South Korea and co-workers investigated the signals that trigger monocytes to attach to artery walls, and how SIRT1 might prevent attachment. After identifying the signals, further testing in mice fed a high-fat diet showed that SIRT1 strongly decreased plaque formation. These findings illuminate the causes and progression of atherosclerosis and may help identify better treatments.
Databáze: OpenAIRE
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