The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Chronic Apoptosis of Vascular Smooth Muscle Cells Accelerates Atherosclerosis and Promotes Calcification and Medial Degeneration
Open accessAbstract
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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“The micro-calcification (speckles of 0.5-15 µ m) sometimes observed within the lipid pool of PITs, typically close to the border with the media, may also be a consequence of VSMC apoptosis 51 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [51]
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Vascular smooth muscle cells in atherosclerosis
Bennett, M. R., Sinha, S., & Owens, G. K. (2016) · Circulation Research · doi:10.1161/circresaha.115.306361 · Cited by 2,179
Self-citationVascular smooth muscle cells in atherosclerosis
Basatemur, G. L., Jørgensen, H. F., Clarke, M. C. H., Bennett, M. R., & Mallat, Z. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-019-0227-9 · Cited by 1,099
Self-citationMedial vascular calcification revisited: review and perspectives
Lanzer, P., Boehm, M., Sorribas, V., Thiriet, M., Janzen, J., Zeller, T., Hilaire, C. S., & Shanahan, C. M. (2014) · European Heart Journal · doi:10.1093/eurheartj/ehu163 · Cited by 742
The vascular smooth muscle cell in arterial pathology: a cell that can take on multiple roles
Lacolley, P. J., Regnault, V., Nicoletti, A., Li, Z., & Michel, J. (2012) · Cardiovascular Research · doi:10.1093/cvr/cvs135 · Cited by 744
Vascular smooth muscle cell death, autophagy and senescence in atherosclerosis
Grootaert, M. O. J., Moulis, M., Roth, L., Martinet, W., Vindis, C., Bennett, M. R., & De Meyer, G. R. Y. (2018) · Cardiovascular Research · doi:10.1093/cvr/cvy007 · Cited by 606
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Metadata
- 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
- Venue
- Circulation Research
- Published
- 2008-06-20
- Volume
- 102
- Issue
- 12
- Pages
- 1529-1538
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- 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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