CoChat
Sign Up
Cited by 625Atherosclerosis and Cardiovascular DiseasesAutophagy in Disease and TherapyCell death mechanisms and regulation

Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis

Open access
Grootaert, Mandy O J, Moulis, Manon, Roth, Lynn, Martinet, Wim, Vindis, Cécile, Bennett, Martin R, De Meyer, Guido R Y·2018·Cardiovascular Research
DOI 10.1093/cvr/cvy007
Open this paper in CoChat — free accountOpen PDF

Abstract

In the present review, we describe the causes and consequences of loss of vascular smooth muscle cells (VSMCs) or their function in advanced atherosclerotic plaques and discuss possible mechanisms such as cell death or senescence, and induction of autophagy to promote cell survival. We also highlight the potential use of pharmacological modulators of these processes to limit plaque progression and/or improve plaque stability. VSMCs play a pivotal role in atherogenesis. Loss of VSMCs via initiation of cell death leads to fibrous cap thinning and promotes necrotic core formation and calcification. VSMC apoptosis is induced by pro-inflammatory cytokines, oxidized low density lipoprotein, high levels of nitric oxide and mechanical injury. Apoptotic VSMCs are characterized by a thickened basal lamina surrounding the cytoplasmic remnants of the VSMC. Inefficient clearance of apoptotic VSMCs results in secondary necrosis and subsequent inflammation. A critical determinant in the VSMC stress response and phenotypic switching is autophagy, which is activated by various stimuli, including reactive oxygen and lipid species, cytokines, growth factors and metabolic stress. Successful autophagy stimulates VSMC survival, whereas reduced autophagy promotes age-related changes in the vasculature. Recently, an interesting link between autophagy and VSMC senescence has been uncovered. Defective VSMC autophagy accelerates not only the development of stress-induced premature senescence but also atherogenesis, albeit without worsening plaque stability. VSMC senescence in atherosclerosis is likely a result of replicative senescence and/or stress-induced premature senescence in response to DNA damaging and/or oxidative stress-inducing stimuli. The finding that VSMC senescence can promote atherosclerosis further illustrates that normal, adequate VSMC function is crucial in protecting the vessel wall against atherosclerosis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/cvr/cvy007

Cites

95 of 95 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • Targeting autophagy has bidirectional therapeutic potential in vascular pathologies: autophagy induction may protect against endothelial dysfunction and hypertension, while autophagy-inducing stimuli promote vascular smooth muscle cell proliferation leading to vascular remodeling.

    “Furthermore, targeting autophagy demonstrates bidirectional therapeutic potential in vascular pathologies.While autophagy induction may protect against endothelial dysfunction and hypertension, autophagy-inducing stimuli promote VSMC proliferation, leading to vascular remodeling.In contrast, rapamycin-based drugs are used to treat arterial stenosis 5 .”

    From Targeting autophagy to treat neointimal hyperplasia in vascular disease (2025) · cites this paper as [5]

    Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.

    Experimental — accuracy not yet measured

  • Autophagy is a critical determinant of vascular smooth muscle cell plasticity and phenotypic switching.

    “Indeed, autophagy is a critical determinant of VSMC plasticity and phenotypic switching.”

    From Targeting autophagy to treat neointimal hyperplasia in vascular disease (2025) · cites this paper as [5]

  • Defective autophagy is implicated in the pathogenesis of several vascular diseases.

    “Defective autophagy has therefore been implicated in the pathogenesis of several vascular diseases 5 .”

    From Targeting autophagy to treat neointimal hyperplasia in vascular disease (2025) · cites this paper as [5]

  • Impaired or excessive autophagy may lead to cell death, neointimal formation and atherosclerotic plaque instability.

    “While physiological autophagy promotes VSMC survival, impaired or excessive autophagy may lead to cell death, neointimal formation and atherosclerotic plaque instability 5 .”

    From Targeting autophagy to treat neointimal hyperplasia in vascular disease (2025) · cites this paper as [5]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Related

Authors
Grootaert, M. O. J., Moulis, M., Roth, L., Martinet, W., Vindis, C., Bennett, M. R., & De Meyer, G. R. Y.
Affiliations
  • University of Cambridge (GB)
  • Inserm (FR)
  • University of Antwerp (BE)
  • Laboratory of Physiopharmacology, University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium
ORCID
Venue
Cardiovascular Research
Publisher
Oxford University Press (OUP)
Published
2018-01-18
Volume
114
Issue
4
Pages
622-634
ISSN
  • 0008-6363 (ISSN-L)
  • 1755-3245
DOI
10.1093/cvr/cvy007
OpenAlex
W2792785502
Cited by
606
References
95
Citations by year
2026: 57 · 2025: 80 · 2024: 108 · 2023: 73 · 2022: 112 · 2021: 70 · 2020: 54 · 2019: 32 · 2018: 19
FWCI
4.48
Type
journal article
Language
en
Open access
Locations
  • Cardiovascular Research (publishedVersion)
  • PubMed (publishedVersion)
  • Lirias (KU Leuven) (submittedVersion, other-oa)
  • Digital Access to Libraries (submittedVersion, other-oa)
Funders
  • FWO (G.0412.16 N)
  • British Heart Foundation (RG/13/14/30314 and PG/16/11/32021)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Keywords
vascular smooth muscle cells, atherosclerosis, apoptosis, autophagy, cellular senescence, stress-induced premature senescence, replicative senescence, plaque stability, fibrous cap thinning, necrotic core, calcification, oxidized LDL, nitric oxide, inflammatory cytokines, autophagy modulators, VSMC phenotypic switching
MeSH terms
Animals, Arteries, Autophagy, Humans, Muscle, Smooth, Vascular, Phenotype, Signal Transduction, Cellular Senescence, Myocytes, Smooth Muscle, Cell Proliferation, Atherosclerosis, Plaque, Atherosclerotic

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