Interleukin-1β has atheroprotective effects in advanced atherosclerotic lesions of mice

Abstract

Despite decades of research, our understanding of the processes controlling late-stage atherosclerotic plaque stability remains poor. A prevailing hypothesis is that reducing inflammation may improve advanced plaque stability, as recently tested in the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS) trial, in which post-myocardial infarction subjects were treated with an IL-1β antibody. Here, we performed intervention studies in which smooth muscle cell (SMC) lineage-tracing Apoe mice with advanced atherosclerosis were treated with anti-IL-1β or IgG control antibodies. Surprisingly, we found that IL-1β antibody treatment between 18 and 26 weeks of Western diet feeding induced a marked reduction in SMC and collagen content, but increased macrophage numbers in the fibrous cap. Moreover, although IL-1β antibody treatment had no effect on lesion size, it completely inhibited beneficial outward remodeling. We also found that SMC-specific knockout of Il1r1 (encoding IL-1 receptor type 1) resulted in smaller lesions nearly devoid of SMCs and lacking a fibrous cap, whereas macrophage-selective loss of IL-1R1 had no effect on lesion size or composition. Taken together, these results show that IL-1β has multiple beneficial effects in late-stage murine atherosclerosis, including promotion of outward remodeling and formation and maintenance of an SMC- and collagen-rich fibrous cap.

Rutaecarpine derivative R3 attenuates atherosclerosis via inhibiting NLRP3 inflammasome‐related inflammation and modulating cholesterol transport

“…22 RUT exerts anti-inflammatory effects by inhibiting inflammatory mediators, 16 although the exact anti-inflammatory mechanism is poorly understood. 22 RUT exerts anti-inflammatory effects by inhibiting inflammatory mediators, 16 although the exact anti-inflammatory mechanism is poorly understood.…”

The proinflammatory cytokines IL‐1β and TNF‐α modulate corneal epithelial wound healing through p16Ink4a suppressing STAT3 activity

“…Mounting evidence has shown that proinflammatory cytokines, particularly interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), are involved in inflammation, immunity, tissue repair, and cancer (Aarreberg et al, 2019;Bachus et al, 2019;Balkwill, 2009;Gomez et al, 2018;Johnson, O'Keefe, & Grandis, 2018;Kang, Tanaka, Narazaki, & Kishimoto, 2019;Stock, Jama, Hansen, & Wicks, 2019). In the cornea, proinflammatory cytokines are pleiotropic, wherein they are associated with corneal immune response, angiogenesis, chemotaxis, wound healing, and corneal diseases (Torres & Kijlstra, 2001;Wilson et al, 2001;Yang et al, 2019).…”

Fibrous caps in atherosclerosis form by Notch-dependent mechanisms common to arterial media development

“…The entire root was scanned by acquiring multiple images and stitching them in a Z-stack, and quantification was performed in the plaque in the left coronary sinus, which is the most advanced in mouse models of atherosclerosis. Nuclei with surrounding ACTA2 signal were counted in the arterial media, plaque, and the cap region, defined as the area within 30 μm from the lumen as previously described (13). Nuclei with SOX9 signal were identified in plaques using an ImageJ macro and checked manually for correctness.…”