Expression of anti and pro-inflammatory genes in human endothelial cells activated by 25-hydroxycholesterol: A comparison of rivaroxaban and dabigatran.
Administration, Oral
Anticoagulants
/ pharmacology
Atherosclerosis
/ drug therapy
Atrial Fibrillation
/ drug therapy
Cytokines
/ genetics
Dabigatran
/ pharmacology
Endothelial Cells
/ drug effects
Human Umbilical Vein Endothelial Cells
/ drug effects
Humans
Hydroxycholesterols
/ administration & dosage
Interleukin-18
/ genetics
Interleukin-23
/ genetics
Oxysterols
/ administration & dosage
RNA, Messenger
/ genetics
Rivaroxaban
/ pharmacology
Transforming Growth Factor beta
/ genetics
25-hydroxycholesterol
dabigatran
endothelial cells
inflammatory markers
rivaroxaban
Journal
Clinical and experimental pharmacology & physiology
ISSN: 1440-1681
Titre abrégé: Clin Exp Pharmacol Physiol
Pays: Australia
ID NLM: 0425076
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
28
04
2022
received:
15
12
2021
accepted:
09
05
2022
pubmed:
17
5
2022
medline:
14
7
2022
entrez:
16
5
2022
Statut:
ppublish
Résumé
Atherosclerosis is associated with a haemostatic imbalance characterized by excessive activation of pro-inflammatory and pro-coagulant pathways. Non-vitamin K antagonists oral anticoagulant (NOACs) may reduce the incidence of cardiovascular events, cerebral ischemia, thromboembolic events and atherosclerosis. Chronic inflammation, vascular proliferation and the development of atherosclerosis is also influenced by 25-hydroxycholesterol (25-OHC). The aim of the study was to assess the effect of rivaroxaban and dabigatran on the messenger RNA (mRNA) expression of anti-inflammatory cytokines transforming growth factor β (TGF-β), interleukin (IL)-37, IL-35 as well as of pro-inflammatory cytokines IL-18 and IL-23, in endothelial cells damaged by 25-OHC. Human umbilical vascular endothelial cells (HUVECs) were treated with 25-OHC (10 μg/mL), rivaroxaban (100, 500 ng/mL), dabigatran (100, 500 ng/mL), 25-OHC + rivaroxaban, and 25-OHC + dabigatran. The mRNA expression of TGF-β, IL-37, IL-35 subunits EBI3 and p35, IL-18, and IL-23 was analysed using real-time polymerase chain reaction (PCR). The results showed that 25-OHC decreased TGF-β and IL-37 mRNA expression and increased EBI3, p35, IL-18, IL-23 mRNA expression in endothelial cell as compared to an untreated control (P < .05). Messenger RNA expression of TGF-β and IL-37 significantly increased following stimulation with rivaroxaban and dabigatran as compared to an untreated control (P < .01). In HUVECs pre-treated with oxysterol, rivaroxaban and dabigatran increased mRNA expression of TGF-β, IL-37 and decreased mRNA expression of EBI3, p35, IL-23 and IL-18 as compared to 25-OHC (P < .01). Our finding suggests that both rivaroxaban and dabigatran inhibit the inflammatory activation caused by oxysterol in vitro.
Identifiants
pubmed: 35577580
doi: 10.1111/1440-1681.13668
doi:
Substances chimiques
Anticoagulants
0
Cytokines
0
Hydroxycholesterols
0
Interleukin-18
0
Interleukin-23
0
Oxysterols
0
RNA, Messenger
0
Transforming Growth Factor beta
0
25-hydroxycholesterol
767JTD2N31
Rivaroxaban
9NDF7JZ4M3
Dabigatran
I0VM4M70GC
Types de publication
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
805-812Informations de copyright
© 2022 John Wiley & Sons Australia, Ltd.
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