Reduced Apoptosis and Plaque Necrosis in Advanced Atherosclerotic Lesions of Apoe-/- and Ldlr-/- Mice Lacking CHOP

Edward Thorp, Gang Li, Tracie A. Seimon, George Kuriakose, David Ron, Ira Tabas*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

269 Scopus citations

Abstract

Endoplasmic reticulum (ER) stress is a hallmark of advanced atherosclerosis, but its causative role in plaque progression is unknown. In vitro studies have implicated the ER stress effector CHOP in macrophage apoptosis, a process involved in plaque necrosis in advanced atheromata. To test the effect of CHOP deficiency in vivo, aortic root lesions of fat-fed Chop+/+;Apoe-/- and Chop-/-;Apoe-/- mice were analyzed for size and morphology. Despite similar plasma lipoproteins, lesion area was 35% smaller in Chop-/-;Apoe-/- mice. Most importantly, plaque necrosis was reduced by ∼50% and lesional apoptosis by 35% in the CHOP-deficient mice. Similar results were found in fat-fed Chop-/-;Ldlr-/- versus Chop+/+;Ldlr-/- mice. Thus, CHOP promotes plaque growth, apoptosis, and plaque necrosis in fat-fed Apoe-/- and Ldlr-/- mice. These data provide direct evidence for a causal link between the ER stress effector CHOP and plaque necrosis and suggest that interventions weakening this arm of the UPR may lessen plaque progression.

Original languageEnglish (US)
Pages (from-to)474-481
Number of pages8
JournalCell Metabolism
Volume9
Issue number5
DOIs
StatePublished - May 6 2009

Keywords

  • HUMDISEASE

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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