Steroidogenic acute regulatory protein (StAR) and atherogenesis

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)peer-review

2 Citations (Scopus)

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 languageEnglish
Title of host publicationCholesterol Transporters of the START Domain Protein Family in Health and Disease
EditorsB. Clark, D. Stocco
PublisherSpringer Nature
Pages99-117
Number of pages19
ISBN (Electronic)9781493911127
ISBN (Print)1493911120, 9781493911110
DOIs
Publication statusPublished - 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

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