Eating the dead to keep atherosclerosis at bay
Open accessAbstract
Atherosclerosis is the primary cause of coronary heart disease (CHD), ischemic stroke, and peripheral arterial disease. Despite effective lipid-lowering therapies and prevention programs, atherosclerosis is still the leading cause of mortality in the United States. Moreover, the prevalence of CHD in developing countries worldwide is rapidly increasing at a rate expected to overtake those of cancer and diabetes. Prominent risk factors include the hardening of arteries and high levels of cholesterol, which lead to the initiation and progression of atherosclerosis. However, cell death and efferocytosis are critical components of both atherosclerotic plaque progression and regression, yet, few currently available therapies focus on these processes. Thus, understanding the causes of cell death within the atherosclerotic plaque, the consequences of cell death, and the mechanisms of apoptotic cell clearance may enable the development of new therapies to treat cardiovascular disease. Here, we review how endoplasmic reticulum stress and cholesterol metabolism lead to cell death and inflammation, how dying cells affect plaque progression, and how autophagy and the clearance of dead cells ameliorates the inflammatory environment of the plaque. In addition, we review current research aimed at alleviating these processes and specifically targeting therapeutics to the site of the plaque.
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Atherosclerosis is at least in part a disease of chronic inflammation, not unlike T2D.
“Therefore, atherosclerosis is at least in part a disease of chronic inflammation, not unlike T2D.”
From Understanding the Holobiont: How Microbial Metabolites Affect Human Health and Shape the Immune System (2017) · cites this paper as Brophy et al., 2017
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“This destabilizes the entire plaque, facilitating rupture and subsequent formation of an embolus that may result in myocardial infarction, stroke, or other forms of cardiovascular disease (Brophy et al., 2017; Frostegård, 2013; Moore et al., 2013).”
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PECAM1, COL4A2, PHACTR1, and LMOD1 Gene Polymorphisms in Patients with Unstable Angina
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Roles of extracellular vesicles derived from immune cells in atherosclerosis
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The potential targets in immunotherapy of atherosclerosis
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The Pathogenic Role of Foam Cells in Atherogenesis: Do They Represent Novel Therapeutic Targets?
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From a dirty breath to atherosclerosis: Ozone pollution and neutrophil extracellular traps (NETs)
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Mohd Idrus, F. N., Ahmad, N. S., Hoe, C. H., Azlan, M., Norfuad, F. A., Yusof, Z., Wan Isa, W. Y. H., Mohamed Ali, A. A., & Yvonne-Τee, G. B. (2021) · Figshare · doi:10.6084/m9.figshare.14299353
Mathematical modeling of atherosclerosis
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- Authors
- Brophy, M. L., Dong, Y., Wu, H., Rahman, H. N. A., Song, K., & Chen, H.
- Affiliations
- Boston Children's Hospital (US)
- Corresponding author
- Chen, Hong
- Venue
- Frontiers in Cardiovascular Medicine
- Publisher
- Frontiers Media SA
- Published
- 2017-01-30
- Volume
- 4
- Pages
- 2-2
- ISSN
- 2297-055X (ISSN-L)
- PMC
- PMC5277199
- OpenAlex
- W2580081338
- Cited by
- 68
- References
- 145
- Citations by year
- 2025: 5 · 2024: 10 · 2023: 8 · 2022: 10 · 2021: 16 · 2020: 5 · 2019: 4 · 2018: 6 · 2017: 4
- FWCI
- 0.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Cardiovascular Medicine (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (R01HL-093242, R01HL-118676, P20 RR018758, 1F23HL121954-01, 1F31HL127982-01)
- Oklahoma Center for the Advancement of Science and Technology (HR09-116, AR11-043, HR14-056)
- U.S. Department of Defense (W81XWH-11-1-00226)
- American Heart Association (Established Investigator Award, 12SDG8760002, 13POST16940008, 13POST17270006, 15PRE21400010)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- atherosclerosis, efferocytosis, endoplasmic reticulum stress, cholesterol metabolism, autophagy, atherosclerotic plaque, inflammation, plaque regression, plaque progression, cell death, coronary artery disease, ischemic stroke, peripheral arterial disease
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