Cited by 133Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthLipid metabolism and disorders

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Elevated Triglyceride Content Diminishes the Capacity of High Density Lipoprotein to Deliver Cholesteryl Esters via the Scavenger Receptor Class B Type I (SR-BI)

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Greene, Diane J., Skeggs, Josephine W., Morton, Richard E.·2001·Journal of Biological Chemistry

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Abstract

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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Background
Mechanisms of HDL deficiency in mice overexpressing human apoA-II
Julve, J., Escolá‐Gil, J. C., Ribas, V., González‐Sastre, F., Ordóñez‐Llanos, J., Sánchez‐Quesada, J. L., & Blanco‐Vaca, F. (2002) · Journal of Lipid Research · doi:10.1194/jlr.m200081-jlr200 · Cited by 32
“It is worthy to note that HDL composition affects selective cholesteryl ester uptake because triglyceride and cholesteryl esters compete for SR-BI-mediated cellular uptake ( 31 ).”
Background
Serum Triglyceride Levels and Cardiovascular Disease Events in Koreans
Kim, E. H., Lee, J. B., Kim, S., Jo, M., Hwang, J. Y., Bae, S. J., Jung, C. H., Lee, W. J., Park, J., Park, G., et al. (2015) · Cardiology · doi:10.1159/000380941 · Cited by 30
Normal HDL Cholesterol Efflux and Anti-Inflammatory Capacities in Type 2 Diabetes Despite Lipidomic Abnormalities
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Comment on: Triglyceride-to-HDL cholesterol ratio: Predictive value for CHD severity and new-onset heart failure
İşçen, S., & Zhenyue, C. (2013) · Herz · doi:10.1007/s00059-013-3840-0 · Cited by 28
Polyphenols can Potentially Prevent Atherosclerosis and Cardiovascular Disease by Modulating Macrophage Cholesterol Metabolism
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Effect of DanQi Pill on PPARα, lipid disorders and arachidonic acid pathway in rat model of coronary heart disease
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“The cholesterol kit (COD-PAP Method), triglyceride kit (GPO-PAP Method), direct HDL kit and direct LDL kit were purchased from BiosinaTechnologies Inc. Evaluation of mRNA expressions of molecules involved in lipid metabolism by polymerase chain reaction (PCR) Expressions of LPL and CD36 in heart tissues were determine…”
BackgroundInfluential
A specific plasma lipid signature associated with high triglycerides and low HDL cholesterol identifies residual CAD risk in patients with chronic coronary syndrome
Giorgi, N. D., Michelucci, E., Smit, J. M., Scholte, A. J. H. A., Mahdiui, M. E., Knuuti, J. M., Buechel, R. R., Teresińska, A., Pizzi, M. N., Roque, A., et al. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.11.013 · Cited by 26
High Density Lipoprotein: Assembly, Structure, Cargo, and Functions
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“Therefore, SR-B1 has the ability to facilitate selective uptake CE and other lipids from both HDL and LDL into the cell, and either uptake or donate unesterified cholesterol [124, 136–142].”
Background
Postprandial lipemia enhances the capacity of large HDL2 particles to mediate free cholesterol efflux via SR-BI and ABCG1 pathways in type IIB hyperlipidemia
Julia, Z., Duchêne, E., Fournier, N., Bellanger, N., Chapman, M. J., Goff, W. L., & Guérin, M. (2010) · Journal of Lipid Research · doi:10.1194/jlr.p009746 · Cited by 26
Determinants of HDL Cholesterol Efflux Capacity after Virgin Olive Oil Ingestion: Interrelationships with Fluidity of HDL Monolayer
Fernández‐Castillejo, S., Rubió, L., Hernáez, Á., Catalán, Ú., Pedret, A., Valls, R. M., Mosele, J. I., Covas, M., Remaley, A. T., Castañer, O., et al. (2017) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201700445 · Cited by 25
“[52] In summary, by using a model as VOO consumption in which improvements in HDL characteristics and functionality have been reported,[10,17–24] we looked for the major determinants of the CEC.”
BackgroundInfluential
Arterial Stiffness Determinants for Primary Cardiovascular Prevention among Healthy Participants
Vallée, A. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11092512 · Cited by 26
“Furthermore, elevated triglyceride levels can promote atherosclerosis through the scavenger receptor class B Type 1 (SR-BI) by impairing the capacity of high-density lipoprotein to deliver cholesteryl esters [58].”
Background
Early Signs of Atherogenic Features in the HDL Lipidomes of Normolipidemic Patients Newly Diagnosed with Type 2 Diabetes
Kostara, C. E., Ferrannini, E., Bairaktari, E. T., Papathanasiou, A. I., Elisaf, M., & Tsimihodimos, V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21228835 · Cited by 22
“the RCT, these particles negatively influence other important metabolic pathways involved in heart disease, including a reduced capacity for lecithin; less cholesterol acyltransferase (LCAT) to convert free cholesterol to cholesterol esters; and a diminished capacity to deliver cholesterol esters to hepatic cells via…”
Background
Protein Mediators of Sterol Transport Across Intestinal Brush Border Membrane
Brown, J. M., & Yu, L. (2010) · Sub-cellular biochemistry/Subcellular biochemistry · doi:10.1007/978-90-481-8622-8_12 · Cited by 22
“Additionally, SR-BI can also promote selective uptake of free sterols, phospholipids, triglycerides, and cholesteryl ethers (Stangl et al., 1999, Urban et al., 2000, Greene et al., 2001).”
Background
Metabolic disorders and inflammation are associated with familial combined hyperlipemia
Díaz-Ruiz, M., Martínez-Triguero, M. L., López‐Ruiz, A., la Cruz, F. F.-D., Bañuls, C., & Hernández‐Mijares, A. (2018) · Clinica Chimica Acta · doi:10.1016/j.cca.2018.09.009 · Cited by 19
Triglycerides: How Much Credit Do They Deserve?
Kohli, P., & Cannon, C. P. (2012) · Medical Clinics of North America · doi:10.1016/j.mcna.2011.11.006 · Cited by 17
Triglyceride enrichment of HDL does not alter HDL-selective cholesteryl ester clearance in rabbits
Rashid, S., Uffelman, K. D., Barrett, P. H. R., Vicini, P., Adeli, K., & Lewis, G. F. (2001) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)31688-6 · Cited by 16
Scavenger Receptor Class B, Type I: A Promising Immunotherapy Target
Fioravanti, J., Medina‐Echeverz, J., & Berraondo, P. (2011) · Immunotherapy · doi:10.2217/imt.10.104 · Cited by 15
Feedback Inhibition of Human Scavenger Receptor Class B Type I Gene Expression by Glucocorticoid in Adrenal and Ovarian Cells
Mavridou, S., Venihaki, M., Rassouli, O., Tsatsanis, C., & Kardassis, D. (2010) · Endocrinology · doi:10.1210/en.2009-1302 · Cited by 15
Cardiovascular risk profile in burn survivors
Leung, B., Younger, J. F., Stockton, K. A., Müller, M. J., & Paratz, J. D. (2017) · Burns · doi:10.1016/j.burns.2017.07.010 · Cited by 13
Pedoman Tatalaksana Dislipidemia PERKI 2013
Erwinanto, E., Santoso, A., Putranto, J. N., Tedjasukmana, P., Suryawan, R., Rifqi, S., & Kasiman, S. (2015) · Indonesian Journal of Cardiology · doi:10.30701/ijc.v34i4.385 · Cited by 14
Improved plasma cholesterol efflux capacity from human macrophages in patients with hyperalphalipoproteinemia
Khoury, P. E., Plengpanich, W., Frisdal, É., Goff, W. L., Khovidhunkit, W., & Guérin, M. (2014) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2014.02.032 · Cited by 12
Enterocyte Fatty Acid Handling Proteins and Chylomicron Formation
Cifarelli, V., & Abumrad, N. A. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-809954-4.00048-7 · Cited by 16
Triglyceride and Cardiovascular Disease
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Reduced Reverse Cholesterol Transport Efficacy in Healthy Men with Undesirable Postprandial Triglyceride Response
Motte, A., Gall, J., Salem, J., Dasque, E., Lebot, M., Frisdal, É., Galier, S., Villard, E. F., Bouaziz-Amar, É., Lacorte, J., et al. (2020) · Biomolecules · doi:10.3390/biom10050810 · Cited by 12
“Those observations are entirely consistent with earlier studies showing that the CETP-mediated reduction in the CE/TG ratio in HDL particles due to a TG enrichment, as observed in subjects from GHigh as compared to GLow or during postprandial lipemia (Table 3) is associated with a significant decrease in the SR-BI-med…”
Result
Early time‐restricted feeding improves high‐density lipoprotein amount and function in nonhuman primates, without effects on body composition
Kavanagh, K., Bashore, A. C., Davis, M. A., Jorgensen, M. J., McLouth, C. J., Beavers, D. P., & Parks, J. S. (2022) · Obesity · doi:10.1002/oby.23564 · Cited by 9
“Our study points to a clear shift toward larger HDL particle size, which can result from more TG content, and TG is known to interfere with CEC function [35].”
Background
Modification of CETP function by changing its substrate preference: a new paradigm for CETP drug design
Morton, R. E., & Izem, L. (2015) · Journal of Lipid Research · doi:10.1194/jlr.m056333 · Cited by 10
Self-citation
The beneficial effects of HDL-C on atherosclerosis: rationale and clinical results
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Associations of Abdominal and Cardiovascular Adipose Tissue Depots With HDL Metrics in Midlife Women: the SWAN Study
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Metabolismus und Funktion der Lipoproteine hoher Dichte (HDL)
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CD36 and Intestinal Fatty Acid Absorption
Nassir, F., & Abumrad, N. A. (2009) · Immunology Endocrine & Metabolic Agents - Medicinal Chemistry · doi:10.2174/187152209788009823 · Cited by 9
Adrenocorticotrophic hormone retarded metabolism of low‐density lipoprotein in rats
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Intravascular hemolysis triggers NAFLD characterized by a deregulation of lipid metabolism and lipophagy blockade
Rayego‐Mateos, S., Morgado‐Pascual, J. L., García‐Caballero, C., Lázaro, I., Sala‐Vila, A., Opazo-Ríos, L., Mas, S., Egido, J., Ruiz‐Ortega, M., & Moreno, J. A. (2023) · The Journal of Pathology · doi:10.1002/path.6161 · Cited by 8
“The SR-BI is a scavenger receptor associated with the selective uptake or influx of HDL-derived cholesteryl esters and other lipids from HDLs and LDLs to cells [76,77].”
Background
Hypertriglyceridemic waist: missing piece of the global cardiovascular risk assessment puzzle?
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Triglycerides and Cardiovascular Disease : A Scientific Statement From the
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Enterocyte Fatty Acid Handling Proteins and Chylomicron Formation
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Metabolism of high density lipoprotein apolipoprotein A‐I and cholesteryl ester in insulin resistant dog: a stable isotope study
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APOC3: Triglycerides do matter
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“(2) Triglyceride enrichment of high density lipoprotein (HDL) particles makes them dysfunctional.(5) (3) Postprandial triglycerides has been reported to induce apoptosis, and increase the expression of pro-inflammatory genes.”
Background
Arterial stiffness and biological parameters: A decision tree machine learning application in hypertensive participants
Vallée, A. (2023) · PLoS ONE · doi:10.1371/journal.pone.0288298 · Cited by 4
“damaging capacity of HDL to secrete cholesteryl esters [57].”
Background
Role of LCAT and Apo A-I in Newly Diagnosed HIV Patients
Mirajkar, A., Nikam, S., Nikam, P., & Patil, G. (2016) · Indian Journal of Clinical Biochemistry · doi:10.1007/s12291-016-0631-4 · Cited by 3
“If this situation persists over long period of time, it may contribute to the increased risk of atherosclerosis [21].”
Background

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)
DOI: 10.1074/jbc.m008725200
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: cc-by
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by/4.0/ (vor, 7191 d)
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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Elevated Triglyceride Content Diminishes the Capacity of High Density Lipoprotein to Deliver Cholesteryl Esters via the Scavenger Receptor Class B Type I (SR-BI)

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