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Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host
Open accessAbstract
Infection and inflammation induce the acute-phase response (APR), leading to multiple alterations in lipid and lipoprotein metabolism. Plasma triglyceride levels increase from increased VLDL secretion as a result of adipose tissue lipolysis, increased de novo hepatic fatty acid synthesis, and suppression of fatty acid oxidation. With more severe infection, VLDL clearance decreases secondary to decreased lipoprotein lipase and apolipoprotein E in VLDL. In rodents, hypercholesterolemia occurs attributable to increased hepatic cholesterol synthesis and decreased LDL clearance, conversion of cholesterol to bile acids, and secretion of cholesterol into the bile. Marked alterations in proteins important in HDL metabolism lead to decreased reverse cholesterol transport and increased cholesterol delivery to immune cells. Oxidation of LDL and VLDL increases, whereas HDL becomes a proinflammatory molecule. Lipoproteins become enriched in ceramide, glucosylceramide, and sphingomyelin, enhancing uptake by macrophages. Thus, many of the changes in lipoproteins are proatherogenic. The molecular mechanisms underlying the decrease in many of the proteins during the APR involve coordinated decreases in several nuclear hormone receptors, including peroxisome proliferator-activated receptor, liver X receptor, farnesoid X receptor, and retinoid X receptor. APR-induced alterations initially protect the host from the harmful effects of bacteria, viruses, and parasites. However, if prolonged, these changes in the structure and function of lipoproteins will contribute to atherogenesis.
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“Decreases in HDL and LDL cholesterol, as well as RCT, belong to the metabolic adaptations found in APR during inflammatory attack67.”
From Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses (2016) · cites this paper as [67]
In the citing paper
“Many acute conditions, including surgical trauma, myocardial infarction and inflammation, induce the systemic acute phase reaction (APR), with acute phase protein production in the liver as an integral part of the host defence response.”
From Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses (2016) · cites this paper as [67]
In the citing paper
“In addition to changes in protein synthesis, also lipid metabolism undergoes significant modifications in APR6667.”
From Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses (2016) · cites this paper as [67]
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Metadata
- Authors
- Khovidhunkit, W., Kim, M.-S., Memon, R. A., Shigenaga, J. K., Moser, A. H., Feingold, K. R., & Grunfeld, C.
- Affiliations
- Chulalongkorn University (TH)
- San Francisco VA Medical Center (US)
- Corresponding author
- Feingold, Kenneth R.
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2004-07
- Volume
- 45
- Issue
- 7
- Pages
- 1169-1196
- ISSN
- 0022-2275 (ISSN-L)
- OpenAlex
- W2340325420
- Cited by
- 1,481
- References
- 388
- Citations by year
- 2026: 61 · 2025: 66 · 2024: 68 · 2023: 79 · 2022: 88 · 2021: 90 · 2020: 72 · 2019: 76 · 2018: 73 · 2017: 76 · 2016: 55 · 2015: 54 · 2014: 74 · 2013: 74 · 2012: 72
- FWCI
- 9.80
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Greater South Information System
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK66999, R01DK066999, DK-49900)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- atherogenesis, acute phase response, infection, inflammation, lipid metabolism, lipoprotein metabolism, triglycerides, VLDL secretion, hepatic fatty acid synthesis, lipoprotein lipase, apolipoprotein E, hypercholesterolemia, hepatic cholesterol synthesis, LDL clearance, HDL metabolism, reverse cholesterol transport, LDL oxidation, ceramide, sphingomyelin, macrophage uptake, nuclear receptors, peroxisome proliferator-activated receptors, liver X receptor, farnesoid X receptor, retinoid X receptor, proatherogenic lipoproteins
- MeSH terms
- Animals, Humans, Immunity, Innate, Infections, Inflammation, Lipids, Lipoproteins, Receptors, Cytoplasmic and Nuclear, Lipid Metabolism
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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