Cited by 68Atherosclerosis and Cardiovascular DiseasesPhagocytosis and Immune RegulationCholesterol and Lipid Metabolism

Eating the dead to keep atherosclerosis at bay

Open access
Brophy, Megan L., Dong, Yunzhou, Wu, Hao, Rahman, H. N. Ashiqur, Song, Kai, Chen, Hong·2017·Frontiers in Cardiovascular Medicine

Abstract

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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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
Published
2017-01-30
Volume
4
Pages
2-2
ISSN
2297-055X (ISSN-L)
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
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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