Senescent intimal foam cells are deleterious at all stages of atherosclerosis

Bennett G. Childs, Darren J Baker, Tobias Wijshake, Cheryl A Conover, Judith Campisi, Jan Van Deursen

Research output: Contribution to journalArticle

237 Scopus citations

Abstract

Advanced atherosclerotic lesions contain senescent cells, but the role of these cells in atherogenesis remains unclear. Using transgenic and pharmacological approaches to eliminate senescent cells in atherosclerosis-prone low-density lipoprotein receptor-deficient (Ldlr-/-) 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 of atherosclerosis.

Original languageEnglish (US)
Pages (from-to)472-477
Number of pages6
JournalScience
Volume354
Issue number6311
DOIs
StatePublished - Oct 28 2016

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ASJC Scopus subject areas

  • Medicine(all)
  • General

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