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Steroidogenic Acute Regulatory Protein (StAR) and Atherogenesis

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Cholesterol Transporters of the START Domain Protein Family in Health and Disease

Abstract

Atherosclerosis, the primary cause of coronary heart disease, is characterised by a low-grade unresolved inflammation associated with accumulation of cholesterol and cholesteryl-ester laden macrophages within the intima of the vessel wall. Steroidogenic acute regulatory protein (StAR/STARD1) is endogenously expressed, and regulated, in a number of vascular tissues, including endothelial cells and monocyte-macrophages where it is thought to traffic cholesterol from the outer to the inner mitochondrial membrane, determining the rate at which substrate is supplied to sterol 27-hydroxylase (CYP27A1). The CYP27A1 enzyme converts cholesterol to oxysterol derivatives, which act as activating ligands for nuclear Liver X Receptors, master regulators of lipid metabolism and inflammatory responses. Forced overexpression of StAR/STARD1 in macrophages and endothelial cells increases the cholesterol efflux process mediated by adenosine triphosphate (ATP)-binding cassette transporters (ABCA1/G1) and apolipoprotein acceptors, and inhibits nuclear factor-κB signalling, resulting in repression of an array of inflammatory genes. Thus, StAR/STARD1 may represent a novel target for treatment of atherosclerosis and coronary heart disease.

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Notes

  1. 1.

    Taylor Janice, Allen Anne-Marie, Borthwick Faye, Graham Annette (2009) Q-PCR analysis of StAR-induced genes involved in lipid and lipoprotein metabolism. Glasgow Caledonian University.

  2. 2.

    Borthwick Faye, Graham Annette (2009) Gonadotropin-dependent regulation of genes involved in the cholesterol efflux pathway. Glasgow Caledonian University.

Abbreviations

ACAT:

Acyl CoA: Cholesterol AcylTransferase

ACBD:

Acyl CoA Binding Domain Protein

ANT:

Adenine Nucleotide Transporter

Apo:

Apolipoprotein

ASTAD3A:

ATPase Family AAA Domain-containing Protein 3A

CD:

Cluster of Differentiation

CETP:

Cholesteryl Ester Transfer Protein

ChREBP:

Binding Protein

CTX:

Cerebrotendinous Xanthomatosis

COX:

Cyclooxygenase

CXCL16:

Chemokine (C-X-C motif) Ligand 16

CYP11A1:

Cytochrome P450 Side Chain Cleavage Enzyme

CYP27A1:

Sterol 27-Hydroxylase

CYP51A1:

Lanosterol 14α-methylase

DR:

Direct Repeat

ER:

Estrogen Receptor

FAS:

Fatty Acid Synthase

GM-CSF:

Granulocyte Macrophage Colony Stimulating Factor

HDL:

High-density Lipoprotein

HDL-C:

HDL-cholesterol

HMG CoA Reductase:

3-Hydroxy 3-MethylGlutaryl CoA Reductase

IFN:

Interferon

IL:

Interleukin

iNOS:

Inducible Nitric Oxide Synthase

LCAT:

Lecithin:Cholesterol AcylTransferase

LDL:

Low Density Lipoprotein

LOX-1:

Lectin-like Oxidized LDL Receptor

LPS:

Lipopolysaccharide

LXR:

Liver X Receptor

LXRE:

Response Element

LDL:

Low Density Lipoprotein

MCP:

Monocyte Chemotactic Protein

M-CSF:

Macrophage Colony Stimulating Factor

MLN64; STARD3:

Metastatic Lymph Node 64

NF-κB:

Nuclear Factor Kappa B

NCoR:

Nuclear Receptor Co-Repressor

PKA:

Protein Kinase A

PLTP:

Phospholipid Transfer Protein

PPAR:

Peroxisome Proliferator Activated Receptor

RXR:

Retinoid X Receptor

SCD:

Stearoyl CoA Desaturase

SERM:

Selective Estrogen Receptor Modulator

SMRT:

Silencing Mediator of Retinoid and Thyroid receptors

SR-AI/AII:

Scavenger Receptor AI/AII

SRE:

Sterol Regulatory Element

SREBP:

Binding Protein

StAR; STARD1:

Steroidogenic Acute Regulatory protein

STARD3:

StAR-related Lipid Transfer Domain 3 Protein

TGF:

Transforming Growth Factor

TNF:

Tumour Necrosis Factor

TSPO:

18 kDa Translocator Protein

VCAM:

Vascular Cell Adhesion Molecule

VDAC:

Voltage Dependent Anion Channel

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Authors and Affiliations

  1. Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK

    Annette Graham Ph.D. & Janice Taylor Ph.D.

  2. Metabolic and Cardiovascular Diseases Laboratory, Alberta Diabetes Institute, University of Alberta, Edmonton, AB, Canada

    Faye Borthwick Ph.D.

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  1. Annette Graham Ph.D.
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  2. Faye Borthwick Ph.D.
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Correspondence to Annette Graham Ph.D. .

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Editors and Affiliations

  1. Biochemistry and Molecular Biology, University of Louisville School of Medicine, Louisville, Kentucky, USA

    Barbara J. Clark

  2. Cell Biology and Biochemistry, Texas Tech Univ. Health Sciences Center, Lubbock, Texas, USA

    Douglas M. Stocco

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Graham, A., Borthwick, F., Taylor, J. (2014). Steroidogenic Acute Regulatory Protein (StAR) and Atherogenesis. In: Clark, B., Stocco, D. (eds) Cholesterol Transporters of the START Domain Protein Family in Health and Disease. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1112-7_5

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