Stage-dependent differential effects of interleukin-1 isoforms on experimental atherosclerosis. (30th January 2019)

• Record Type: Journal Article
• Authors: Vromman, Amélie; Ruvkun, Victoria; Shvartz, Eugenia; Wojtkiewicz, Gregory; Santos Masson, Gustavo; Tesmenitsky, Yevgenia; Folco, Eduardo; Gram, Hermann; Nahrendorf, Matthias; Swirski, Filip K; Sukhova, Galina K; Libby, Peter
• Is Part Of: European heart journal. Volume 40:Number 30(2019)
• Page Start: 2482
• Page End: 2491
• Publication Date: 2019-01-30
• Subjects: Interleukin-1 -- Atherosclerosis -- Arterial remodelling -- Inflammation; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehz008
• Languages: English
• ISSNs: 0195-668X

Abstract

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. 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. 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.