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

205 Citations (Scopus)

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

Fingerprint

Tunica Intima
Foam Cells
Atherosclerosis
Elastic Tissue
LDL Receptors
Metalloproteases
Atherosclerotic Plaques
Chemokines
Macrophages
Pharmacology
Pathology
Cytokines

ASJC Scopus subject areas

  • Medicine(all)
  • General

Cite this

Senescent intimal foam cells are deleterious at all stages of atherosclerosis. / Childs, Bennett G.; Baker, Darren J; Wijshake, Tobias; Conover, Cheryl A; Campisi, Judith; Van Deursen, Jan.

In: Science, Vol. 354, No. 6311, 28.10.2016, p. 472-477.

Research output: Contribution to journalArticle

Childs, Bennett G. ; Baker, Darren J ; Wijshake, Tobias ; Conover, Cheryl A ; Campisi, Judith ; Van Deursen, Jan. / Senescent intimal foam cells are deleterious at all stages of atherosclerosis. In: Science. 2016 ; Vol. 354, No. 6311. pp. 472-477.
@article{228527bfc06645aeb15268c4c8b03352,
title = "Senescent intimal foam cells are deleterious at all stages of atherosclerosis",
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.",
author = "Childs, {Bennett G.} and Baker, {Darren J} and Tobias Wijshake and Conover, {Cheryl A} and Judith Campisi and {Van Deursen}, Jan",
year = "2016",
month = "10",
day = "28",
doi = "10.1126/science.aaf6659",
language = "English (US)",
volume = "354",
pages = "472--477",
journal = "Science",
issn = "0036-8075",
publisher = "American Association for the Advancement of Science",
number = "6311",

}

TY - JOUR

T1 - Senescent intimal foam cells are deleterious at all stages of atherosclerosis

AU - Childs, Bennett G.

AU - Baker, Darren J

AU - Wijshake, Tobias

AU - Conover, Cheryl A

AU - Campisi, Judith

AU - Van Deursen, Jan

PY - 2016/10/28

Y1 - 2016/10/28

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84992730363&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84992730363&partnerID=8YFLogxK

U2 - 10.1126/science.aaf6659

DO - 10.1126/science.aaf6659

M3 - Article

C2 - 27789842

AN - SCOPUS:84992730363

VL - 354

SP - 472

EP - 477

JO - Science

JF - Science

SN - 0036-8075

IS - 6311

ER -