Cited by 357Phagocytosis and Immune RegulationAtherosclerosis and Cardiovascular DiseasesCholesterol and Lipid Metabolism

Mertk Receptor Mutation Reduces Efferocytosis Efficiency and Promotes Apoptotic Cell Accumulation and Plaque Necrosis in Atherosclerotic Lesions of Apoe −/− Mice

Open access
Thorp, Edward, Cui, Dongying, Schrijvers, Dorien M., Kuriakose, George, Tabas, Ira·2008·Arteriosclerosis, Thrombosis, and Vascular Biology

Abstract

Objective— Atherosclerotic plaques that are prone to disruption and acute thrombotic vascular events are characterized by large necrotic cores. Necrotic cores result from the combination of macrophage apoptosis and defective phagocytic clearance (efferocytosis) of these apoptotic cells. We previously showed that macrophages with tyrosine kinase-defective Mertk receptor (Mertk KD ) have a defect in phagocytic clearance of apoptotic macrophages in vitro. Herein we test the hypothesis that the Mertk KD mutation would result in increased accumulation of apoptotic cells and promote necrotic core expansion in a mouse model of advanced atherosclerosis. Methods and Results— Mertk KD ; Apoe −/− mice and control Apoe −/− mice were fed a Western-type diet for 10 or 16 weeks, and aortic root lesions were analyzed for apoptosis and plaque necrosis. We found that the plaques of the Mertk KD ; Apoe −/− mice had a significant increase in terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive apoptotic cells. Most importantly, there were more non-macrophage-associated apoptotic cells in the Mertk KD lesions, consistent with defective efferocytosis. The more advanced (16-week) Mertk KD ; Apoe −/− plaques were more necrotic, consistent with a progression from apoptotic cell accumulation to plaque necrosis in the setting of a defective efferocytosis receptor. Conclusion— In a mouse model of advanced atherosclerosis, mutation of the phagocytic Mertk receptor promotes the accumulation of apoptotic cells and the formation of necrotic plaques. These data are consistent with the notion that a defect in an efferocytosis receptor can accelerate the progression of atherosclerosis and suggest a novel therapeutic target to prevent advanced plaque progression and its clinical consequences.

Integrity signals

Registry

Crossref · 10.1161/atvbaha.108.167197

Cites

38 of 38 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Mice lacking MERTK or expressing a constitutively inactive MERTK have larger plaques and greater necrotic core area than control mice.

    “Conversely, mice lacking MERTK or expressing a constitutively inactive form of MERTK show larger plaque size and increased necrotic core area compared with control mice196,197.”
  • Impaired macrophage efferocytosis enhances atherogenesis and atherosclerotic plaque instability.

    “The impaired ability of macrophage efferocytosis would enhance atherogenesis [139,140,141] and atherosclerotic plaque instability [142,143,144].”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Thorp, E., Cui, D., Schrijvers, D. M., Kuriakose, G., & Tabas, I.
Affiliations
Columbia University (US)
Venue
Arteriosclerosis, Thrombosis, and Vascular Biology
Published
2008-08
Volume
28
Issue
8
Pages
1421-1428
ISSN
  • 1079-5642 (ISSN-L)
  • 1524-4636
OpenAlex
W2122693935
Cited by
357
References
38
Citations by year
2026: 22 · 2025: 16 · 2024: 25 · 2023: 13 · 2022: 19 · 2021: 21 · 2020: 24 · 2019: 22 · 2018: 25 · 2017: 26 · 2016: 22 · 2015: 19 · 2014: 19 · 2013: 23 · 2012: 19
FWCI
5.84
Type
journal article
Language
en
Open access
Locations
  • Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Heart, Lung, and Blood Institute (HL-75662, P01HL054591, R01HL075662, HL 54591)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Keywords
efferocytosis, macrophage apoptosis, ApoE-deficient mice, plaque progression, Western diet, aortic root lesions, therapeutic target
MeSH terms
c-Mer Tyrosine Kinase, Animals, Aorta, Apolipoproteins E, Disease Models, Animal, Foam Cells, Male, Mutation, Phagocytosis, Proto-Oncogene Proteins, Apoptosis, Mice, Knockout, In Situ Nick-End Labeling, Receptor Protein-Tyrosine Kinases, Atherosclerosis, Mice

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 ›

Are you an author, or do you see a problem with this page? Request a review