The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Elevated Triglyceride Content Diminishes the Capacity of High Density Lipoprotein to Deliver Cholesteryl Esters via the Scavenger Receptor Class B Type I (SR-BI)
Open accessAbstract
The selective uptake of high density lipoprotein (HDL) cholesteryl ester (CE) by the scavenger receptor class B type I (SR-BI) is well documented. However, the effect of altered HDL composition, such as occurs in hyperlipidemia, on this important process is not known. This study investigated the impact of variable CE and triglyceride (TG) content on selective uptake. CE selective uptake by Y1 and HepG2 cells was strongly affected by modification of either the CE or TG content of HDL. Importantly, TG, like CE, was selectively taken up by a dose-dependent, saturable process in these cells. As shown by ACTH up-regulation and receptor overexpression experiments, SR-BI mediated the selective uptake of both CE and TG. With in vitro modified HDLs of varying CE and TG composition, the selective uptake of CE and TG was dependent on the abundance of each lipid within the HDL particle. Furthermore, total selective uptake (CE + TG) remained constant, indicating that these lipids competed for cellular uptake. These data support a novel mechanism whereby SR-BI binds HDL and mediates the incorporation of a nonspecific portion of the HDL lipid core. In this way, TG directly affects the ability of HDL to donate CE to cells. Processes that raise the TG/CE ratio of HDL will impair the delivery of CE to cells via this receptor and may compromise the efficiency of sterol balancing pathways such as reverse cholesterol transport.
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“In this regard, elevated TG and insulin resistance may both impair HDL function37-39 and predate the development of diabetes.40”
From Is Isolated Low High-Density Lipoprotein Cholesterol a Cardiovascular Disease Risk Factor?: New Insights From the Framingham Offspring Study (2016) · cites this paper as [38]
In the citing paper
“Experimental studies suggest that hypertriglyceridemic HDL may be dysfunctional, 55,56 that small, dense LDL particles may be more susceptible to oxidative modification, 57,58 and that an increased number of atherogenic particles may adversely influence CVD risk 59 ; however, no clinical outcome trials to date have determined whether normalization of particle composition or reduction of particle”
From Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association (2011) · cites this paper as [55]
Citations
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Research works printed but not linked: 1
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Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association
Miller, M., Stone, N. J., Ballantyne, C., Bittner, V., Criqui, M. H., Ginsberg, H. N., Goldberg, A. C., Howard, W. J., Jacobson, M. S., Kris-Etherton, P. M., et al. (2011) · Circulation · doi:10.1161/cir.0b013e3182160726 · Cited by 1,871
New Insights Into the Regulation of HDL Metabolism and Reverse Cholesterol Transport
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“Consistent with these findings, HDL capacity to deliver CE to hepatic cells through interaction with SR-BI diminishes as a result of HDL enrichment in TG (Greene et al., 2001).”
ResultMiller, M., Cannon, C. P., Murphy, S. A., Qin, J., Ray, K. K., & Braunwald, E. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2007.10.038 · Cited by 610
Rigotti, A., Miettinen, H. E., & Krieger, M. (2003) · Endocrine Reviews · doi:10.1210/er.2001-0037 · Cited by 435
Metadata
- Authors
- Greene, D. J., Skeggs, J. W., & Morton, R. E.
- Affiliations
- Cleveland Clinic (US)
- Corresponding author
- Morton, Richard E.
- ORCID
- Morton, Richard E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2001-02
- Volume
- 276
- Issue
- 7
- Pages
- 4804-4811
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2053088392
- Cited by
- 133
- References
- 52
- Citations by year
- 2025: 3 · 2023: 3 · 2022: 6 · 2021: 2 · 2020: 5 · 2019: 5 · 2018: 4 · 2017: 7 · 2016: 5 · 2015: 5 · 2014: 7 · 2013: 12 · 2012: 8
- FWCI
- 7.54
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL060934, HL60934)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Keywords
- high-density lipoprotein, scavenger receptor class B type I, cholesteryl ester uptake, triglyceride content, HDL lipid composition, selective uptake, reverse cholesterol transport, sterol balance, hyperlipidemia, receptor overexpression
- MeSH terms
- Animals, Biological Transport, Cell Line, Cholesterol Esters, Humans, Lipoproteins, HDL, Membrane Proteins, Receptors, Immunologic, Substrate Specificity, Transfection, Triglycerides, Receptors, Lipoprotein, CD36 Antigens, COS Cells, Receptors, Scavenger, Scavenger Receptors, Class B
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