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Mechanism of plasma cholesteryl ester transfer in hypertriglyceridemia.
Open accessAbstract
Plasma net cholesteryl ester (CE) transfer and optimum cho- lesteryl ester transfer protein (CETP) activity were determined in primary hypertriglyceridemic (a = 11) and normolipidemic (a = 15) individuals.The hypertriglyceridemic group demon- strated threefold greater net CE transfer leading to enhanced accumulation of CE in VLDL.This increased net transfer was not accompanied by a change in CETP activity.In normolipide- mia, but not in hypertriglyceridemia, net CE transfer correlated with VLDL triglyceride (r = 0.92, P < 0.001).In contrast, net CE transfer in hypertriglyceridemia, but not in normolipide- mia, correlated with CETP activity (r = 0.73, P < 0.01).Correc- tion of hypertriglyceridemia with bezafibrate reduced net CE transfer towards normal and restored the correlation with VLDL triglyceride (r = 0.90, P < 0.005) while suppressing the correlation with CETP activity.That net CE transfer depends on VLDL concentration was confirmed by an increase ofnet CE transfer in normolipidemic plasma supplemented with purified VLDL.Supplementation of purified CETP to normolipidemic plasma did not stimulate net CE transfer.In contrast, net CE transfer was enhanced by addition of CETP to both plasma supplemented with VLDL and hypertriglyceridemic plasma.Thus, in normal subjects, VLDL concentration determines the rate of net CE transfer.CETP becomes rate limiting as VLDL concentration increases, i.e, in hypertriglyceridemia. (J.Clin.Invest.1991.88:2059-2066.)Key words: cholesteryl ester transfer protein * very low density lipoprotein -high density lipoprotein -cardiovascular disease * reverse cholesterol trans- port MO.Bezafibrate (2-[4-[2-[(4-chlorobenzoyl)amino]-ethyl]phenoxy]-2methylpropanoic acid) was obtained from Boehringer Mannheim (for- merly MCP Pharmaceuticals), Livingstone, Scotland. Cholesteryl Ester Transfer in Hypertriglyceridemia 2059
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“Hepatic lipase and cholesterol ester transfer protein contribute to the remodeling processes; whether hepatic lipase or cholesterol ester transfer protein has the predominant effect on the size and density of LDL and HDL particles depends on the triglyceride content of very low-density lipoproteins (VLDL) (27,28).”
From Evaluation and Treatment of Hypertriglyceridemia: An Endocrine Society Clinical Practice Guideline (2012) · cites this paper as [27]
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Metadata
- Authors
- Mann, C. J., Yen, F. T., Grant, A. M., & Bihain, B. E.
- Affiliations
- Louisiana State University (US)
- ORCID
- Yen, F T
- Venue
- Journal of Clinical Investigation
- Published
- 1991-12-01
- Volume
- 88
- Issue
- 6
- Pages
- 2059-2066
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W2114689977
- Cited by
- 339
- References
- 30
- Citations by year
- 2024: 5 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 2 · 2014: 10 · 2013: 1 · 2012: 2
- FWCI
- 17.17
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5p01hl025596-15)
- National Heart, Lung, and Blood Institute (HL255-96)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Keywords
- cholesteryl ester transfer, cholesteryl ester transfer protein, hypertriglyceridemia, VLDL, VLDL triglycerides, reverse cholesterol transport, CETP activity, bezafibrate, lipoprotein metabolism, rate-determining step
- MeSH terms
- Adult, Bezafibrate, Biological Transport, Carrier Proteins, Cholesterol Esters, Glycoproteins, Humans, Lipoproteins, HDL, Lipoproteins, LDL, Lipoproteins, VLDL, Triglycerides, Hypertriglyceridemia, Cholesterol Ester Transfer Proteins
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