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Cited by 480Endoplasmic Reticulum Stress and DiseaseAtherosclerosis and Cardiovascular DiseasesCholesterol and Lipid Metabolism

The Role of Endoplasmic Reticulum Stress in the Progression of Atherosclerosis

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Tabas, Ira·2010·Circulation Research
DOI 10.1161/circresaha.110.224766PMC PMC2951143
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Abstract

Prolonged activation of the endoplasmic reticulum (ER) stress pathway known as the unfolded protein response (UPR) can lead to cell pathology and subsequent tissue dysfunction. There is now ample evidence that the UPR is chronically activated in atherosclerotic lesional cells, particularly advanced lesional macrophages and endothelial cells. The stressors in advanced lesions that can lead to prolonged activation of the UPR include oxidative stress, oxysterols, and high levels of intracellular cholesterol and saturated fatty acids. Importantly, these arterial wall stressors may be especially prominent in the settings of obesity, insulin resistance, and diabetes, all of which promote the clinical progression of atherosclerosis. In the case of macrophages, prolonged ER stress triggers apoptosis, which in turn leads to plaque necrosis if the apoptotic cells are not rapidly cleared. ER stress–induced endothelial cell apoptosis may also contribute to plaque progression. Another potentially important proatherogenic effect of prolonged ER stress is activation of inflammatory pathways in macrophages and, perhaps in response to atheroprone shear stress, endothelial cells. Although exciting work over the last decade has begun to shed light on the mechanisms and in vivo relevance of ER stress–driven atherosclerosis, much more work is needed to fully understand this area and to enable an informed approach to therapeutic translation.

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  • High cholesterol levels, fatty acids, and oxidative stress can trigger ER stress-induced apoptosis of macrophages and endothelial cells associated with atherosclerosis.

    “Moreover, high cholesterol levels, fatty acids, and oxidative stress can trigger ER stress-induced apoptosis of macrophages and endothelial cells associated with atherosclerosis [420].”

    From GANAB and N-Glycans Substrates Are Relevant in Human Physiology, Polycystic Pathology and Multiple Sclerosis: A Review (2022) · cites this paper as [420]

    The macrophage sections describe ER stress-induced apoptosis associated with intracellular cholesterol and saturated fatty acids; Therapeutic Implications links oxidative stress to that apoptosis. The Endothelial Cells section reports that oxidized LDL induces endothelial ER stress and that sustained XBP1 activation can cause endothelial apoptosis, but it does not establish that all three named triggers cause ER stress-induced apoptosis in endothelial cells. The cholesterol evidence also concerns intracellular accumulation, not simply high circulating cholesterol levels. (LLM, conf=0.84)

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Authors
Tabas, I.
Affiliations
Columbia University (US)
Corresponding author
Tabas, Ira
ORCID
Tabas, Ira
Venue
Circulation Research
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2010-10
Volume
107
Issue
7
Pages
839-850
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
DOI
10.1161/circresaha.110.224766
PMC
PMC2951143
OpenAlex
W2073377382
Cited by
480
References
4
Citations by year
2026: 15 · 2025: 17 · 2024: 20 · 2023: 16 · 2022: 22 · 2021: 26 · 2020: 33 · 2019: 26 · 2018: 25 · 2017: 35 · 2016: 33 · 2015: 35 · 2014: 42 · 2013: 44 · 2012: 50
FWCI
3.86
Type
journal article
Language
en
Open access
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Heart, Lung, and Blood Institute (HL087123, P01HL054591, HL054591, HL075662, P01HL087123, R01HL075662)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Endoplasmic Reticulum Stress and Disease
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
endoplasmic reticulum stress, unfolded protein response, atherosclerosis progression, atherosclerotic plaque, macrophages, endothelial cells, oxidative stress, oxysterols, intracellular cholesterol, saturated fatty acids, obesity, insulin resistance, diabetes mellitus, apoptosis, plaque necrosis, inflammation
MeSH terms
Endoplasmic Reticulum, Humans, Macrophages, Stress, Physiological, Apoptosis, Disease Progression, Atherosclerosis, Unfolded Protein Response

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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