Scavenger receptor SR-BI in macrophage lipid metabolism

Ailing Ji; Jason M. Meyer; Lei Cai; Akinwunmi Akinmusire; Maria C. de Beer; Nancy R. Webb; Deneys R. van der Westhuyzen

doi:10.1016/j.atherosclerosis.2011.03.017

Scavenger receptor SR-BI in macrophage lipid metabolism

Ailing Ji, Jason M. Meyer, Lei Cai, Akinwunmi Akinmusire, Maria C. de Beer, Nancy R. Webb, Deneys R. van der Westhuyzen

Pharmacology and Nutritional Sciences

Research output: Contribution to journal › Article › peer-review

55 Scopus citations

Abstract

Objective: To investigate the mechanisms by which macrophage scavenger receptor BI (SR-BI) regulates macrophage cholesterol homeostasis and protects against atherosclerosis. Methods and results: The expression and function of SR-BI was investigated in cultured mouse bone marrow-derived macrophages (BMM). SR-BI, the other scavenger receptors SRA and CD36 and the ATP-binding cassette transporters ABCA1 and ABCG1 were each distinctly regulated during BMM differentiation. SR-BI levels increased transiently to significant levels during culture. SR-BI expression in BMM was reversibly down-regulated by lipid loading with modified LDL; SR-BI was shown to be present both on the cell surface as well as intracellularly. BMM exhibited selective HDL CE uptake, however, this was not dependent on SR-BI or another potential candidate glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1). SR-BI played a significant role in facilitating bidirectional cholesterol flux in non lipid-loaded cells. SR-BI expression enhanced both cell cholesterol efflux and cholesterol influx from HDL, but did not lead to altered cellular cholesterol mass. SR-BI-dependent efflux occurred to larger HDL particles but not to smaller HDL ₃. Following cholesterol loading, ABCA1 and ABCG1 were up-regulated and served as the major contributors to cholesterol efflux, while SR-BI expression was down-regulated. Conclusion: Our results suggest that SR-BI plays a significant role in macrophage cholesterol flux that may partly account for its effects on atherogenesis.

Original language	English
Pages (from-to)	106-112
Number of pages	7
Journal	Atherosclerosis
Volume	217
Issue number	1
DOIs	https://doi.org/10.1016/j.atherosclerosis.2011.03.017
State	Published - Jul 2011

Bibliographical note

Funding Information:
The authors would like to thank Xuebing Wang, Xin Shi, Kathy Forrest and Susan Bridges for excellent technical support. The ABCA1 antibody was generously provided by Dr Michael Hayden. This work was supported by a National Institutes of Health Program Project Grant (PO1HL086670) to D. R. van der Westhuyzen.

Keywords

ABCA1
ABCG1
Cholesterol efflux
HDL
Macrophage
SR-BI

ASJC Scopus subject areas

Cardiology and Cardiovascular Medicine

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10.1016/j.atherosclerosis.2011.03.017

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title = "Scavenger receptor SR-BI in macrophage lipid metabolism",

abstract = "Objective: To investigate the mechanisms by which macrophage scavenger receptor BI (SR-BI) regulates macrophage cholesterol homeostasis and protects against atherosclerosis. Methods and results: The expression and function of SR-BI was investigated in cultured mouse bone marrow-derived macrophages (BMM). SR-BI, the other scavenger receptors SRA and CD36 and the ATP-binding cassette transporters ABCA1 and ABCG1 were each distinctly regulated during BMM differentiation. SR-BI levels increased transiently to significant levels during culture. SR-BI expression in BMM was reversibly down-regulated by lipid loading with modified LDL; SR-BI was shown to be present both on the cell surface as well as intracellularly. BMM exhibited selective HDL CE uptake, however, this was not dependent on SR-BI or another potential candidate glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1). SR-BI played a significant role in facilitating bidirectional cholesterol flux in non lipid-loaded cells. SR-BI expression enhanced both cell cholesterol efflux and cholesterol influx from HDL, but did not lead to altered cellular cholesterol mass. SR-BI-dependent efflux occurred to larger HDL particles but not to smaller HDL 3. Following cholesterol loading, ABCA1 and ABCG1 were up-regulated and served as the major contributors to cholesterol efflux, while SR-BI expression was down-regulated. Conclusion: Our results suggest that SR-BI plays a significant role in macrophage cholesterol flux that may partly account for its effects on atherogenesis.",

keywords = "ABCA1, ABCG1, Cholesterol efflux, HDL, Macrophage, SR-BI",

author = "Ailing Ji and Meyer, {Jason M.} and Lei Cai and Akinwunmi Akinmusire and {de Beer}, {Maria C.} and Webb, {Nancy R.} and {van der Westhuyzen}, {Deneys R.}",

note = "Funding Information: The authors would like to thank Xuebing Wang, Xin Shi, Kathy Forrest and Susan Bridges for excellent technical support. The ABCA1 antibody was generously provided by Dr Michael Hayden. This work was supported by a National Institutes of Health Program Project Grant (PO1HL086670) to D. R. van der Westhuyzen. ",

year = "2011",

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doi = "10.1016/j.atherosclerosis.2011.03.017",

language = "English",

volume = "217",

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AU - Ji, Ailing

AU - Meyer, Jason M.

AU - Cai, Lei

AU - Akinmusire, Akinwunmi

AU - de Beer, Maria C.

AU - Webb, Nancy R.

AU - van der Westhuyzen, Deneys R.

N1 - Funding Information: The authors would like to thank Xuebing Wang, Xin Shi, Kathy Forrest and Susan Bridges for excellent technical support. The ABCA1 antibody was generously provided by Dr Michael Hayden. This work was supported by a National Institutes of Health Program Project Grant (PO1HL086670) to D. R. van der Westhuyzen.

PY - 2011/7

Y1 - 2011/7

N2 - Objective: To investigate the mechanisms by which macrophage scavenger receptor BI (SR-BI) regulates macrophage cholesterol homeostasis and protects against atherosclerosis. Methods and results: The expression and function of SR-BI was investigated in cultured mouse bone marrow-derived macrophages (BMM). SR-BI, the other scavenger receptors SRA and CD36 and the ATP-binding cassette transporters ABCA1 and ABCG1 were each distinctly regulated during BMM differentiation. SR-BI levels increased transiently to significant levels during culture. SR-BI expression in BMM was reversibly down-regulated by lipid loading with modified LDL; SR-BI was shown to be present both on the cell surface as well as intracellularly. BMM exhibited selective HDL CE uptake, however, this was not dependent on SR-BI or another potential candidate glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1). SR-BI played a significant role in facilitating bidirectional cholesterol flux in non lipid-loaded cells. SR-BI expression enhanced both cell cholesterol efflux and cholesterol influx from HDL, but did not lead to altered cellular cholesterol mass. SR-BI-dependent efflux occurred to larger HDL particles but not to smaller HDL 3. Following cholesterol loading, ABCA1 and ABCG1 were up-regulated and served as the major contributors to cholesterol efflux, while SR-BI expression was down-regulated. Conclusion: Our results suggest that SR-BI plays a significant role in macrophage cholesterol flux that may partly account for its effects on atherogenesis.

AB - Objective: To investigate the mechanisms by which macrophage scavenger receptor BI (SR-BI) regulates macrophage cholesterol homeostasis and protects against atherosclerosis. Methods and results: The expression and function of SR-BI was investigated in cultured mouse bone marrow-derived macrophages (BMM). SR-BI, the other scavenger receptors SRA and CD36 and the ATP-binding cassette transporters ABCA1 and ABCG1 were each distinctly regulated during BMM differentiation. SR-BI levels increased transiently to significant levels during culture. SR-BI expression in BMM was reversibly down-regulated by lipid loading with modified LDL; SR-BI was shown to be present both on the cell surface as well as intracellularly. BMM exhibited selective HDL CE uptake, however, this was not dependent on SR-BI or another potential candidate glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1). SR-BI played a significant role in facilitating bidirectional cholesterol flux in non lipid-loaded cells. SR-BI expression enhanced both cell cholesterol efflux and cholesterol influx from HDL, but did not lead to altered cellular cholesterol mass. SR-BI-dependent efflux occurred to larger HDL particles but not to smaller HDL 3. Following cholesterol loading, ABCA1 and ABCG1 were up-regulated and served as the major contributors to cholesterol efflux, while SR-BI expression was down-regulated. Conclusion: Our results suggest that SR-BI plays a significant role in macrophage cholesterol flux that may partly account for its effects on atherogenesis.

KW - ABCA1

KW - ABCG1

KW - Cholesterol efflux

KW - HDL

KW - Macrophage

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SN - 0021-9150

VL - 217

SP - 106

EP - 112

JO - Atherosclerosis

JF - Atherosclerosis

IS - 1

ER -

Scavenger receptor SR-BI in macrophage lipid metabolism

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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