Cited by 396Atherosclerosis and Cardiovascular DiseasesCell death mechanisms and regulationCerebrovascular and Carotid Artery Diseases

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Chronic Apoptosis of Vascular Smooth Muscle Cells Accelerates Atherosclerosis and Promotes Calcification and Medial Degeneration

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Clarke, Murray C.H., Littlewood, Trevor D., Figg, Nichola, Maguire, Janet J., Davenport, Anthony P., Goddard, Martin, Bennett, Martin R.·2008·Circulation Research

DOI 10.1161/circresaha.108.175976

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Abstract

Vascular smooth muscle cell (VSMC) accumulation is implicated in plaque development. In contrast, VSMC apoptosis is implicated in plaque rupture, coagulation, vessel remodeling, medial atrophy, aneurysm formation, and calcification. Although VSMC apoptosis accompanies multiple pathologies, there is little proof of direct causality, particularly with the low levels of VSMC apoptosis seen in vivo. Using a mouse model of inducible VSMC–specific apoptosis, we demonstrate that low-level VSMC apoptosis during either atherogenesis or within established plaques of apolipoprotein (Apo)E −/− mice accelerates plaque growth by two-fold, associated with features of plaque vulnerability including a thin fibrous cap and expanded necrotic core. Chronic VSMC apoptosis induced development of calcified plaques in younger animals and promoted calcification within established plaques. In addition, VSMC apoptosis induced medial expansion, associated with increased elastic lamina breaks, and abnormal matrix deposition reminiscent of cystic medial necrosis in humans. VSMC apoptosis prevented outward remodeling associated with atherosclerosis resulting in marked vessel stenosis. We conclude that VSMC apoptosis is sufficient to accelerate atherosclerosis, promote plaque calcification and medial degeneration, prevent expansive remodeling, and promote stenosis in atherosclerosis.

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10.1161/res.87.11.1055 · DOI
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Authors: Clarke, M. C. H., Littlewood, T. D., Figg, N., Maguire, J. J., Davenport, A. P., Goddard, M., & Bennett, M. R.
Affiliations: University of Cambridge (GB)
ORCID: Clarke, Murray C.H.
Littlewood, Trevor D.
Maguire, Janet J.
Davenport, Anthony P.
Goddard, Martin
Bennett, Martin R.
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2008-06-20
Volume: 102
Issue: 12
Pages: 1529-1538
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/circresaha.108.175976
OpenAlex: W2136324267
Cited by: 396
References: 40
Citations by year: 2026: 10 · 2025: 23 · 2024: 18 · 2023: 24 · 2022: 22 · 2021: 27 · 2020: 21 · 2019: 17 · 2018: 20 · 2017: 24 · 2016: 17 · 2015: 22 · 2014: 32 · 2013: 21 · 2012: 26
FWCI: 9.73
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Circulation Research (publishedVersion)
PubMed (publishedVersion)
Funders: NIHR Biomedical Research Centre, Royal Marsden NHS Foundation Trust/Institute of Cancer Research
National Institute for Health and Care Research
British Heart Foundation (PG/06/024/20354, PS/02/001, PG/05/127/19872, RG04/001, PG/06/024)
University of Cambridge
Cambridge University Hospitals
Topics: Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cerebrovascular and Carotid Artery Diseases
Keywords: vascular smooth muscle cell apoptosis, atherosclerosis, plaque calcification, cystic medial necrosis, medial degeneration, plaque vulnerability, fibrous cap thinning, necrotic core, vascular remodeling, stenosis, ApoE-deficient mice, elastic lamina
MeSH terms: Actins, Animals, Aorta, Thoracic, Aortic Diseases, Apolipoproteins E, Calcinosis, Constriction, Pathologic, Diphtheria Toxin, Mice, Transgenic, Necrosis, Recombinant Fusion Proteins, Vasoconstriction, Minor Histocompatibility Antigens, Cytokines, Apoptosis, Tunica Media, Mice, Knockout, Disease Progression, Amino Acid Substitution, Tumor Suppressor Proteins, Myocytes, Smooth Muscle, Intercellular Signaling Peptides and Proteins, Atherosclerosis, Mice, Heparin-binding EGF-like Growth Factor

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Chronic Apoptosis of Vascular Smooth Muscle Cells Accelerates Atherosclerosis and Promotes Calcification and Medial Degeneration

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