Regulation of signal transduction by HDL

Research output: Contribution to journalReview articlepeer-review

61 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 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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