Oxidized Low-Density Lipoprotein Is Associated With Apoptosis of Vascular Smooth Muscle Cells in Human Atherosclerotic Plaques

Okura, Yoshifumi; Brink, Marijke; Itabe, Hiroyuki; Scheidegger, Kathrin J.; Kalangos, Afksendiyos; Delafontaine, Patrice

doi:10.1161/01.cir.102.22.2680

Cited by 126Atherosclerosis and Cardiovascular DiseasesCell death mechanisms and regulationCholesterol and Lipid Metabolism

Oxidized Low-Density Lipoprotein Is Associated With Apoptosis of Vascular Smooth Muscle Cells in Human Atherosclerotic Plaques

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Okura, Yoshifumi, Brink, Marijke, Itabe, Hiroyuki, Scheidegger, Kathrin J., Kalangos, Afksendiyos, Delafontaine, Patrice·2000·Circulation

DOI 10.1161/01.cir.102.22.2680

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Abstract

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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oxLDL promotes apoptosis signaling in vascular smooth muscle cells and contributes to atherosclerotic plaques.
“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]
The Abstract reports that oxLDL increased the proapoptotic protein BAX in cultured VSMCs, and the Discussion reports oxLDL alongside BAX and apoptotic VSMCs in plaques. The Discussion says these findings strongly suggest a role in apoptosis and that oxLDL most likely contributes to lipid-core formation; it does not establish the claim’s unqualified causal contribution to plaques. (LLM, conf=0.84)
Experimental — accuracy not yet measured
Uptake of OxLDL and formation of VSMC-derived foam cells has been linked to induction of VSMC death by apoptosis.
“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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Authors: Okura, Y., Brink, M., Itabe, H., Scheidegger, K. J., Kalangos, A., & Delafontaine, P.
Affiliations: University Hospital of Geneva (CH)
University of Geneva (CH)
ORCID: Okura, Yoshifumi
Brink, Marijke
Itabe, Hiroyuki
Delafontaine, Patrice
Venue: Circulation
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2000-11-28
Volume: 102
Issue: 22
Pages: 2680-2686
ISSN: 0009-7322 (ISSN-L)
1524-4539
DOI: 10.1161/01.cir.102.22.2680
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
Health Sciences › Medicine › Surgery › 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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Oxidized Low-Density Lipoprotein Is Associated With Apoptosis of Vascular Smooth Muscle Cells in Human Atherosclerotic Plaques

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