The DOI matches its Crossref record; 35 of the 35 references it cites were found in a registry or an index.
Oxidized Low-Density Lipoprotein Is Associated With Apoptosis of Vascular Smooth Muscle Cells in Human Atherosclerotic Plaques
Open accessAbstract
Background —Cytotoxic oxidized LDL (oxLDL) has been shown to promote apoptosis in cultured vascular smooth muscle cells (VSMCs). We investigated the localization of oxLDL and its association with apoptosis and the expression of apoptosis-related proteins in early and advanced atherosclerotic lesions. Methods and Results —Atherosclerotic plaques (n=23) from patients undergoing aortic, carotid, or femoral arterial surgery were studied. In early lesions, oxLDL was located predominantly in the superficial intima and in the media just beneath the internal elastic lamina. Medial VSMCs staining positive for oxLDL showed expression of BAX, a proapoptotic protein of the BCL-2 family. Apoptosis, as detected by DNA in situ terminal deoxynucleotidyl transferase end-labeling (TUNEL), was not present in these early lesions. In advanced plaques, areas of the intima positive for oxLDL showed lower α-smooth muscle actin immunoreactivity ( P <0.01) and higher BAX immunoreactivity ( P <0.05). Furthermore, these areas showed an increased number of apoptotic VSMCs ( P <0.01). Western blot analysis revealed that oxLDL increases BAX expression in cultured human coronary VSMCs. Conclusions —We conclude that in early atherosclerotic lesions, oxLDL-positive VSMCs express BAX, which increases the susceptibility of these cells to undergo apoptosis. This could be important in our understanding of the transition of early lesions into advanced atherosclerotic plaques, which are characterized by regions of cell death. In advanced plaques, oxLDL-positive areas of the intima show higher BAX immunoreactivity and TUNEL-positive VSMCs, and this may contribute to plaque instability and rupture.
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“The oxLDL has been shown to promote apoptosis signaling in the vascular smooth muscle cells and contributes to atherosclerotic plaques [143].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [143]
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“For example, uptake of OxLDL and formation of VSMC-derived foam cells has been linked to induction of VSMC death by apoptosis 118 , and free cholesterol in the lipid pool may be derived from dead VSMC 119 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [118]
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Cited by
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Vascular 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
Expression, Regulation, and Function of IGF-1, IGF-1R, and IGF-1 Binding Proteins in Blood Vessels
Delafontaine, P., Song, Y., & Li, Y. (2003) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000105902.89459.09 · Cited by 543
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Oxidized low-density lipoprotein-induced apoptosis
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Metadata
- Authors
- Okura, Y., Brink, M., Itabe, H., Scheidegger, K. J., Kalangos, A., & Delafontaine, P.
- Affiliations
- University Hospital of Geneva (CH)
- University of Geneva (CH)
- Venue
- Circulation
- Published
- 2000-11-28
- Volume
- 102
- Issue
- 22
- Pages
- 2680-2686
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2161543197
- Cited by
- 126
- References
- 35
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 8 · 2017: 3 · 2016: 5 · 2015: 3 · 2014: 3 · 2013: 2 · 2012: 2
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion, other-oa)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (47035)
- National Institutes of Health (5r01hl047035-07)
- National Heart, Lung, and Blood Institute (HL-45317, HL-47035)
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- oxidized LDL, vascular smooth muscle cell apoptosis, atherosclerotic plaque, Bax, Bcl-2 family proteins, plaque vulnerability, plaque rupture, alpha-smooth muscle actin, advanced atherosclerosis, plaque progression
- MeSH terms
- Actins, Aged, Arteriosclerosis, Cell Line, Female, Humans, Immunohistochemistry, Lipoproteins, LDL, Male, Muscle, Smooth, Vascular, Proto-Oncogene Proteins, Blotting, Western, Apoptosis, Proto-Oncogene Proteins c-bcl-2, In Situ Nick-End Labeling, bcl-2-Associated X Protein
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