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Stage-dependent differential effects of interleukin-1 isoforms on experimental atherosclerosis.
- Source :
-
European heart journal [Eur Heart J] 2019 Aug 07; Vol. 40 (30), pp. 2482-2491. - Publication Year :
- 2019
-
Abstract
- Aims: Targeting interleukin-1 (IL-1) represents a novel therapeutic approach to atherosclerosis. CANTOS demonstrated the benefits of IL-1β neutralization in patients post-myocardial infarction with residual inflammatory risk. Yet, some mouse data have shown a prominent role of IL-1α rather than IL-1β in atherosclerosis, or even a deleterious effect of IL-1 on outward arterial remodelling in atherosclerosis-susceptible mice. To shed light on these disparate results, this study investigated the effect of neutralizing IL-1α or/and IL-1β isoforms starting either early in atherogenesis or later in ApoE-/- mice with established atheroma.<br />Methods and Results: The neutralization of IL-1α or of both IL-1 isoforms impaired outward remodelling during early atherogenesis as assessed by micro-computed tomographic and histologic assessment. In contrast, the neutralization of IL-1β did not impair outward remodelling either during early atherogenesis or in mice with established lesions. Interleukin-1β inhibition promoted a slant of blood monocytes towards a less inflammatory state during atherogenesis, reduced the size of established atheromata, and increased plasma levels of IL-10 without limiting outward remodelling of brachiocephalic arteries.<br />Conclusion: This study established a pivotal role for IL-1α in the remodelling of arteries during early experimental atherogenesis, whereas IL-1β drives inflammation during atherogenesis and the evolution of advanced atheroma in mice.<br /> (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Animals
Arteritis metabolism
Disease Models, Animal
Interleukin-1alpha antagonists & inhibitors
Interleukin-1alpha blood
Interleukin-1beta antagonists & inhibitors
Interleukin-1beta blood
Male
Mice
Mice, Knockout
Monocytes metabolism
Plaque, Atherosclerotic metabolism
Atherosclerosis metabolism
Interleukin-1alpha metabolism
Interleukin-1beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1522-9645
- Volume :
- 40
- Issue :
- 30
- Database :
- MEDLINE
- Journal :
- European heart journal
- Publication Type :
- Academic Journal
- Accession number :
- 30698710
- Full Text :
- https://doi.org/10.1093/eurheartj/ehz008