High-density lipoproteins and ATP-binding cassette transporters as targets for cardiovascular drug therapy.
The recently identified lipid-regulated group of ATP-binding cassette (ABC) transporters acts in various cells and tissues that are important for total body lipid homeostasis. ABCA1 and ABCG1 are key regulators of high-density lipoprotein (HDL) metabolism, acting as protective factors against the development of atherosclerosis. Recent data regarding how these ABC transporters control cholesterol and phospholipid homeostasis have provided valuable insights into the mechanisms of mRNA and protein expression, intracellular trafficking, surface membrane localization and interaction with binding partners and lipoproteins. These studies have identified several potential new targets, including nuclear receptors, ABCA1-interactive proteins and apolipoprotein A-I mimetics, which could be promising tools for raising HDL levels and improving the pharmacological treatment of cardiovascular disease.
Schmitz
Gerd
G
Institute of Clinical Chemistry and Laboratory Medicine, University of Regensburg, Germany. gerd.schmitz@klinik.uni-regensburg.de
Langmann
Thomas
T
D018528:ATP-Binding Cassette Transporters / Q000096:biosynthesis*; D000818:Animals; D000069059:Atorvastatin; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000819:agonists; D022781:Hepatocytes / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology; D006706:Homeostasis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism*; D000071518:Liver X Receptors; D008264:Macrophages / Q000378:metabolism; D009525:Niacin / Q000494:pharmacology; D057093:Orphan Nuclear Receptors; D011758:Pyrroles / Q000494:pharmacology; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists
D018528:ATP-Binding Cassette Transporters; D004268:DNA-Binding Proteins; D006538:Heptanoic Acids; D008075:Lipoproteins, HDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D011758:Pyrroles; D018160:Receptors, Cytoplasmic and Nuclear; D009525:Niacin; D000069059:Atorvastatin