Revisiting Reverse Cholesterol Transport in the Context of High-Density Lipoprotein Free Cholesterol Bioavailability

Research output: Contribution to journalReview article

Dysregulated free cholesterol (FC) metabolism has been implicated in nearly all stages of atherosclerosis, the underlying cause of most cardiovascular disease. According to a widely cited model, the burden of macrophage FC in the arterial wall is relieved by transhepatic reverse cholesterol transport (RCT), which comprises three successive steps: (1) macrophage FC efflux to high-density lipoprotein (HDL) and/or its major protein, apolipoprotein AI; (2) FC esterification by lecithin:cholesterol acyltransferase (LCAT); and (3) HDL-cholesteryl ester (CE) uptake via the hepatic HDL-receptor, scavenger receptor class B type 1 (SR-B1). Recent studies have challenged the validity of this model, most notably the role of LCAT, which appears to be of minor importance. In mice, most macrophage-derived FC is rapidly cleared from plasma (t1/2 < 5 min) without esterification by hepatic uptake; the remainder is taken up by multiple tissue and cell types, especially erythrocytes. Further, some FC is cleared by the nonhepatic transintestinal pathway. Lastly, FC movement among lipid surfaces is reversible, so that a higher-than-normal level of HDL-FC bioavailability-defined by high plasma HDL levels concurrent with a high mol% HDL-FC-leads to the transfer of excess FC to cells in vivo. SR-B1-/- mice provide an animal model to study the mechanistic consequences of high HDL-FC bioavailability that provokes atherosclerosis and other metabolic abnormalities. Future efforts should aim to reduce HDL-FC bioavailability, thereby reducing FC accretion by tissues and the attendant atherosclerosis.

Original languageEnglish (US)
Pages (from-to)47-54
Number of pages8
JournalMethodist DeBakey cardiovascular journal
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2019

PMID: 31049149

Altmetrics

Cite this

Standard

Revisiting Reverse Cholesterol Transport in the Context of High-Density Lipoprotein Free Cholesterol Bioavailability. / Rosales, Corina; Gillard, Baiba K.; Xu, Bingqing; Gotto, Antonio; Pownall, Henry J.

In: Methodist DeBakey cardiovascular journal, Vol. 15, No. 1, 01.01.2019, p. 47-54.

Research output: Contribution to journalReview article

Harvard

Rosales, C, Gillard, BK, Xu, B, Gotto, A & Pownall, HJ 2019, 'Revisiting Reverse Cholesterol Transport in the Context of High-Density Lipoprotein Free Cholesterol Bioavailability' Methodist DeBakey cardiovascular journal, vol. 15, no. 1, pp. 47-54. https://doi.org/10.14797/mdcj-15-1-47

APA

Rosales, C., Gillard, B. K., Xu, B., Gotto, A., & Pownall, H. J. (2019). Revisiting Reverse Cholesterol Transport in the Context of High-Density Lipoprotein Free Cholesterol Bioavailability. Methodist DeBakey cardiovascular journal, 15(1), 47-54. https://doi.org/10.14797/mdcj-15-1-47

Vancouver

Rosales C, Gillard BK, Xu B, Gotto A, Pownall HJ. Revisiting Reverse Cholesterol Transport in the Context of High-Density Lipoprotein Free Cholesterol Bioavailability. Methodist DeBakey cardiovascular journal. 2019 Jan 1;15(1):47-54. https://doi.org/10.14797/mdcj-15-1-47

Author

Rosales, Corina ; Gillard, Baiba K. ; Xu, Bingqing ; Gotto, Antonio ; Pownall, Henry J. / Revisiting Reverse Cholesterol Transport in the Context of High-Density Lipoprotein Free Cholesterol Bioavailability. In: Methodist DeBakey cardiovascular journal. 2019 ; Vol. 15, No. 1. pp. 47-54.

BibTeX

@article{9e6be38cdeb0455f939a89703beacec7,
title = "Revisiting Reverse Cholesterol Transport in the Context of High-Density Lipoprotein Free Cholesterol Bioavailability",
abstract = "Dysregulated free cholesterol (FC) metabolism has been implicated in nearly all stages of atherosclerosis, the underlying cause of most cardiovascular disease. According to a widely cited model, the burden of macrophage FC in the arterial wall is relieved by transhepatic reverse cholesterol transport (RCT), which comprises three successive steps: (1) macrophage FC efflux to high-density lipoprotein (HDL) and/or its major protein, apolipoprotein AI; (2) FC esterification by lecithin:cholesterol acyltransferase (LCAT); and (3) HDL-cholesteryl ester (CE) uptake via the hepatic HDL-receptor, scavenger receptor class B type 1 (SR-B1). Recent studies have challenged the validity of this model, most notably the role of LCAT, which appears to be of minor importance. In mice, most macrophage-derived FC is rapidly cleared from plasma (t1/2 < 5 min) without esterification by hepatic uptake; the remainder is taken up by multiple tissue and cell types, especially erythrocytes. Further, some FC is cleared by the nonhepatic transintestinal pathway. Lastly, FC movement among lipid surfaces is reversible, so that a higher-than-normal level of HDL-FC bioavailability-defined by high plasma HDL levels concurrent with a high mol{\%} HDL-FC-leads to the transfer of excess FC to cells in vivo. SR-B1-/- mice provide an animal model to study the mechanistic consequences of high HDL-FC bioavailability that provokes atherosclerosis and other metabolic abnormalities. Future efforts should aim to reduce HDL-FC bioavailability, thereby reducing FC accretion by tissues and the attendant atherosclerosis.",
keywords = "atherogenesis, cholesterol, free cholesterol bioavailability, high-density lipoproteins, lipid metabolism, reverse cholesterol transport",
author = "Corina Rosales and Gillard, {Baiba K.} and Bingqing Xu and Antonio Gotto and Pownall, {Henry J.}",
year = "2019",
month = "1",
day = "1",
doi = "10.14797/mdcj-15-1-47",
language = "English (US)",
volume = "15",
pages = "47--54",
journal = "Methodist DeBakey Cardiovascular Journal",
issn = "1947-6094",
publisher = "Methodist DeBakey Heart & Vascular Center",
number = "1",

}

RIS

TY - JOUR

T1 - Revisiting Reverse Cholesterol Transport in the Context of High-Density Lipoprotein Free Cholesterol Bioavailability

AU - Rosales, Corina

AU - Gillard, Baiba K.

AU - Xu, Bingqing

AU - Gotto, Antonio

AU - Pownall, Henry J.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Dysregulated free cholesterol (FC) metabolism has been implicated in nearly all stages of atherosclerosis, the underlying cause of most cardiovascular disease. According to a widely cited model, the burden of macrophage FC in the arterial wall is relieved by transhepatic reverse cholesterol transport (RCT), which comprises three successive steps: (1) macrophage FC efflux to high-density lipoprotein (HDL) and/or its major protein, apolipoprotein AI; (2) FC esterification by lecithin:cholesterol acyltransferase (LCAT); and (3) HDL-cholesteryl ester (CE) uptake via the hepatic HDL-receptor, scavenger receptor class B type 1 (SR-B1). Recent studies have challenged the validity of this model, most notably the role of LCAT, which appears to be of minor importance. In mice, most macrophage-derived FC is rapidly cleared from plasma (t1/2 < 5 min) without esterification by hepatic uptake; the remainder is taken up by multiple tissue and cell types, especially erythrocytes. Further, some FC is cleared by the nonhepatic transintestinal pathway. Lastly, FC movement among lipid surfaces is reversible, so that a higher-than-normal level of HDL-FC bioavailability-defined by high plasma HDL levels concurrent with a high mol% HDL-FC-leads to the transfer of excess FC to cells in vivo. SR-B1-/- mice provide an animal model to study the mechanistic consequences of high HDL-FC bioavailability that provokes atherosclerosis and other metabolic abnormalities. Future efforts should aim to reduce HDL-FC bioavailability, thereby reducing FC accretion by tissues and the attendant atherosclerosis.

AB - Dysregulated free cholesterol (FC) metabolism has been implicated in nearly all stages of atherosclerosis, the underlying cause of most cardiovascular disease. According to a widely cited model, the burden of macrophage FC in the arterial wall is relieved by transhepatic reverse cholesterol transport (RCT), which comprises three successive steps: (1) macrophage FC efflux to high-density lipoprotein (HDL) and/or its major protein, apolipoprotein AI; (2) FC esterification by lecithin:cholesterol acyltransferase (LCAT); and (3) HDL-cholesteryl ester (CE) uptake via the hepatic HDL-receptor, scavenger receptor class B type 1 (SR-B1). Recent studies have challenged the validity of this model, most notably the role of LCAT, which appears to be of minor importance. In mice, most macrophage-derived FC is rapidly cleared from plasma (t1/2 < 5 min) without esterification by hepatic uptake; the remainder is taken up by multiple tissue and cell types, especially erythrocytes. Further, some FC is cleared by the nonhepatic transintestinal pathway. Lastly, FC movement among lipid surfaces is reversible, so that a higher-than-normal level of HDL-FC bioavailability-defined by high plasma HDL levels concurrent with a high mol% HDL-FC-leads to the transfer of excess FC to cells in vivo. SR-B1-/- mice provide an animal model to study the mechanistic consequences of high HDL-FC bioavailability that provokes atherosclerosis and other metabolic abnormalities. Future efforts should aim to reduce HDL-FC bioavailability, thereby reducing FC accretion by tissues and the attendant atherosclerosis.

KW - atherogenesis

KW - cholesterol

KW - free cholesterol bioavailability

KW - high-density lipoproteins

KW - lipid metabolism

KW - reverse cholesterol transport

UR - http://www.scopus.com/inward/record.url?scp=85065562490&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065562490&partnerID=8YFLogxK

U2 - 10.14797/mdcj-15-1-47

DO - 10.14797/mdcj-15-1-47

M3 - Review article

VL - 15

SP - 47

EP - 54

JO - Methodist DeBakey Cardiovascular Journal

T2 - Methodist DeBakey Cardiovascular Journal

JF - Methodist DeBakey Cardiovascular Journal

SN - 1947-6094

IS - 1

ER -

ID: 48838742