The effect of lipid-lowering therapies on the pro-inflammatory and anti-inflammatory properties of vascular endothelial cells.
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/ therapeutic use
Rosuvastatin Calcium
/ therapeutic use
Atorvastatin
/ therapeutic use
Anticholesteremic Agents
/ therapeutic use
Interleukin-10
Interleukin-18
/ genetics
Endothelial Cells
Ezetimibe
/ therapeutic use
Atherosclerosis
/ drug therapy
Anti-Inflammatory Agents
/ pharmacology
Transforming Growth Factor beta
RNA, Messenger
/ genetics
Interleukin-23
Drug Therapy, Combination
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2023
2023
Historique:
received:
18
03
2022
accepted:
08
01
2023
entrez:
8
2
2023
pubmed:
9
2
2023
medline:
11
2
2023
Statut:
epublish
Résumé
Atherosclerosis and cardiovascular events can be prevented, or treated, using statin therapy, either alone or in combination with ezetimibe. Chronic inflammation, vascular proliferation, and the development of atherosclerosis are also influenced by 25-hydroxycholesterol (25-OHC). The aim of the study was to compare the direct pleiotropic effects of two commonly-used statins (atorvastatin, rosuvastatin), ezetimibe, and their combinations, on the mRNA expression of pro-inflammatory IL1β, IL-18 and IL-23 and anti-inflammatory TGFβ, IL-35 (EBI3, IL-12 subunits), IL-10 and IL-37, in endothelial cells damaged by 25-OHC. It also analyzed IL-35 expression at the protein level. HUVECs were stimulated with atorvastatin (5 μM), rosuvastatin (10 μM), ezetimibe (1.22 μM), atorvastatin-ezetimibe (5 μM + 1.22 μM) or rosuvastatin-ezetimibe (10 μM + 1.22 μM), with or without pre-incubation with 10 μg/mL 25-OHC. mRNA expression was analyzed by real-time PCR. The protein level of IL-35 was analyzed by ELISA. In the pre-stimulated HUVECs, atorvastatin and rosuvastatin decreased mRNA expression of IL1β, IL-18, IL-23, TGFβ, IL35 and increased mRNA expression of IL-10 and IL-37 compared to 25-OHC. Furthermore, only incubation with rosuvastatin and rosuvastatin-ezetimibe decreased IL-35 mRNA and protein levels. Ezetimibe down-regulated only IL1β. Treatment with rosuvastatin-ezetimibe and atorvastatin-ezetimibe reversed the effect of 25-OHC in IL1β, IL-18 and IL-35 mRNA expression. In conclusion, rosuvastatin has the strongest anti-inflammatory effects and is the best at reducing the effect of oxysterols. Both statins exert a greater anti-inflammatory effect than ezetimibe. The anti-inflammatory effect of the combination therapies appears to be based on the effects of the statins alone and not their combination with ezetimibe.
Identifiants
pubmed: 36753488
doi: 10.1371/journal.pone.0280741
pii: PONE-D-22-07586
pmc: PMC9907854
doi:
Substances chimiques
Hydroxymethylglutaryl-CoA Reductase Inhibitors
0
Rosuvastatin Calcium
83MVU38M7Q
Atorvastatin
A0JWA85V8F
Anticholesteremic Agents
0
Interleukin-10
130068-27-8
Interleukin-18
0
Ezetimibe
EOR26LQQ24
Anti-Inflammatory Agents
0
Transforming Growth Factor beta
0
RNA, Messenger
0
Interleukin-23
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0280741Informations de copyright
Copyright: © 2023 Woźniak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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