Regulation of signal transduction by HDL

Research output: Contribution to journalReview article

59 Scopus citations

Abstract

High density lipoprotein (HDL) cholesterol has direct effects on numerous cell types that influence cardiovascular and metabolic health. These include endothelial cells, vascular smooth-muscle cells, leukocytes, platelets, adipocytes, skeletal muscle myocytes, and pancreatic β cells. The effects of HDL or apoA-I, its major apolipoprotein, occur through the modulation of intracellular calcium, oxygen-derived free-radical production, numerous kinases, and enzymes, including endothelial nitric-oxide synthase (eNOS). ApoA-I and HDL also influence gene expression, particularly genes encoding mediators of inflammation in vascular cells. In many paradigms, the change in intracellular signaling occurs as a result of cholesterol efflux, with the cholesterol acceptor methyl- β -cyclodextrin often invoking responses identical to HDL or apoA-I. The ABC transporters ABCA1 and ABCG1 and scavenger receptor class B, type I (SR-BI) frequently participate in the cellular responses. Structure-function relationships are emerging for signal initiation by ABCA1 and SR-BI, with plasma membrane cholesterol binding by the C-terminal transmembrane domain of SR-BI uniquely enabling it to serve as a sensor of changes in membrane cholesterol. Further investigation of the processes underlying HDL and apoA-I modulation of intracellular signaling will potentially reveal new prophylactic and therapeutic strategies to optimize both cardiovascular and metabolic health.

Original languageEnglish (US)
Pages (from-to)2315-2324
Number of pages10
JournalJournal of lipid research
Volume54
Issue number9
DOIs
StatePublished - Sep 1 2013

Keywords

  • Adenosine triphosphate-binding cassette (ABC) transporter A1 and G1
  • Apolipoprotein A-I, PDZK1
  • High density lipoprotein
  • Scavenger receptor class B, type I

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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