Stage-dependent differential effects of interleukin-1 isoforms on experimental atherosclerosis

Amélie Vromman, Victoria Ruvkun, Eugenia Shvartz, Gregory Wojtkiewicz, Gustavo Santos Masson, Yevgenia Tesmenitsky, Eduardo Folco, Hermann Gram, Matthias Nahrendorf, Filip K. Swirski, Galina K. Sukhova, Peter Libby

Research output: Contribution to journalArticlepeer-review

62 Scopus citations

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.

Original languageEnglish
Pages (from-to)2482-2491
Number of pages10
JournalEuropean Heart Journal
Volume40
Issue number30
DOIs
StatePublished - 7 Aug 2019
Externally publishedYes

Keywords

  • Arterial remodelling
  • Atherosclerosis
  • Inflammation
  • Interleukin-1

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