Targeting macrophage necroptosis for therapeutic and diagnostic interventions in atherosclerosis
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Necroptosis promotes necrotic core and vulnerable atherosclerosis in humans and mice and is a prospective therapeutic and diagnostic tool.
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In Apoe-/- mice, a necrostatin 1-based radiotracer localized specifically to atherosclerotic plaques, and necrostatin 1 treatment reduced lesion size and markers of plaque instability such as necrotic core formation.
“In this study, a radiotracer developed with the small-molecule inhibitor of necroptosis, necrostatin 1, localized specifically to atherosclerotic plaques in Apoe- /- mice, and treatment of Apoe- /- mice with necro-statin 1 reduced atherosclerotic lesion size and markers of plaque instability, such as necrotic core formation169.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [169]
Necroptosis contributes to atherosclerosis and is active in unstable human atherosclerotic lesions.
“Necroptosis has been shown to have a role in atherosclerosis and, importantly, this form of cell death has been shown to be active in unstable atherosclerotic lesions in humans169.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [169]
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- Authors
- Karunakaran, D., Geoffrion, M., Wei, L., Gan, W., Richards, L., Shangari, P., DeKemp, E. M., Beanlands, R. A., Perisic, L., Maegdefessel, L., Hedin, U., Sad, S., Guo, L., Kolodgie, F. D., Virmani, R., Ruddy, T., & Rayner, K. J.
- Affiliations
- Ottawa Heart Institute (CA)
- University of Ottawa Heart Institute, Ottawa, Ontario K1Y4W7, Canada.
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm 171 76, Sweden.
- Department of Medicine, Karolinska Institute, Stockholm 171 76, Sweden.
- Karolinska Institutet (SE)
- University of Ottawa (CA)
- CVPath Institute (US)
- Corresponding author
- Rayner, Katey J.
- ORCID
- Venue
- Science Advances
- Published
- 2016-07
- Volume
- 2
- Issue
- 7
- Pages
- e1600224-e1600224
- ISSN
- 2375-2548 (ISSN-L)
- PMC
- PMC4985228
- OpenAlex
- W2478800195
- Cited by
- 293
- References
- 51
- Citations by year
- 2026: 24 · 2025: 26 · 2024: 41 · 2023: 32 · 2022: 48 · 2021: 30 · 2020: 31 · 2019: 20 · 2018: 16 · 2017: 21 · 2016: 4
- FWCI
- 12.33
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Science Advances (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Canadian Institutes of Health Research (ID0EWEAK8352, MOP130365)
- National Heart, Lung, and Blood Institute (ID0ETKAK8353, HL119047)
- 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
- atherosclerosis, RIPK3, MLKL, necrostatin-1, necrotic core, plaque vulnerability, plaque rupture, low-density lipoprotein, carotid atherosclerosis, radiotracer imaging, ApoE-deficient mice, macrophage cell death, inflammation
- MeSH terms
- Amino Acid Chloromethyl Ketones, Animals, Apolipoproteins E, Bone Marrow Cells, Cells, Cultured, Cholesterol, Coronary Vessels, Humans, Imidazoles, Indoles, Lipoproteins, LDL, Macrophages, Mice, Inbred C57BL, Necrosis, Protein Kinases, Apoptosis, Reactive Oxygen Species, Mice, Knockout, Atherosclerosis, Mice, Receptor-Interacting Protein Serine-Threonine Kinases, Interleukin-1beta
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