Senescent intimal foam cells are deleterious at all stages of atherosclerosis

) mice, we show that these cells are detrimental throughout disease pathogenesis. We find that foamy macrophages with senescence markers accumulate in the subendothelial space at the onset of atherosclerosis, where they drive pathology by increasing expression of key atherogenic and inflammatory cytokines and chemokines. In advanced lesions, senescent cells promote features of plaque instability, including elastic fiber degradation and fibrous cap thinning, by heightening metalloprotease production. Together, these results demonstrate that senescent cells are key drivers of atheroma formation and maturation and suggest that selective clearance of these cells by senolytic agents holds promise for the treatment…

• GF
  Glenn Family Foundation
• GF
  Glenn Foundation for Medical Research
• NY
  New York Stem Cell Foundation
• NI
  National Institutes of Health

  Awards: R01CA96985, CA168709