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.
Original language | English |
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Title of host publication | Cholesterol Transporters of the START Domain Protein Family in Health and Disease |
Editors | B. Clark, D. Stocco |
Publisher | Springer Nature |
Pages | 99-117 |
Number of pages | 19 |
ISBN (Electronic) | 9781493911127 |
ISBN (Print) | 1493911120, 9781493911110 |
DOIs | |
Publication status | Published - 2014 |
Keywords
- diabetes
- atherogenesis
- Endothelial cell
- Macrophage 'foam cell'
- ATP binding cassette transporter
- Cytokine
- Cyclic AMP
- Gonadotropins
- Inflammation
- Apolipoprotein
- Steroidogenic acute regulatory protein
- Leucocytes
- Lipoproteins
- Mitochondrial sterol 27-hydroxylase
- Selective estrogen receptor modulator
- Atherosclerosis
- Oxysterol
- Cholesterol homeostasis
- Apoptosis
- Liver X Receptor
ASJC Scopus subject areas
- General Medicine