title: Regulation of signal transduction by HDL.
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.
authors.affiliation: Division of Pulmonary and Vascular Biology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Chieko
authors.initials: C
authors.lastname: Mineo
authors.forename: Philip W
authors.initials: PW
authors.lastname: Shaul
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000473:pathology; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000473:pathology; D008076:Cholesterol, HDL / Q000378:metabolism*; D006801:Humans; D008659:Metabolic Diseases / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction
chemical_list: D008076:Cholesterol, HDL
keywords: adenosine triphosphate-binding cassette (ABC) transporter A1 and G1; apolipoprotein A-I, PDZK1; high density lipoprotein; scavenger receptor class B, type I