Interleukin-1β promotes atheroprotective changes of advanced atherosclerotic lesions in mice

Despite decades of research, our understanding of the processes controlling late-stage atherosclerotic plaque stability remains poor. Although a prevailing hypothesis is that reducing inflammation may improve advanced plaque stability, direct evidence of this is lacking. Therefore, we performed intervention studies on smooth muscle cell (SMC) lineage tracing Apoe(−/−) mice with advanced atherosclerosis using 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 number in the fibrous cap. There was also no change in lesion size and complete inhibition of beneficial outward remodeling. We also found that SMC-specific Il1r1 KO resulted in smaller lesions nearly devoid of SMC and a fibrous cap whereas macrophage-selective loss of IL-1R1 had no effect on lesion size or composition. Taken together, results show that IL-1β promotes multiple beneficial changes in late-stage murine atherosclerosis including promoting outward remodeling and formation and maintenance of a SMC/collagen-rich fibrous cap.