title: Control of cholesterol metabolism and plasma high-density lipoprotein levels by microRNA-144.
abstract: BACKGROUND
  Foam cell formation because of excessive accumulation of cholesterol by macrophages is a pathological hallmark of atherosclerosis, the major cause of morbidity and mortality in Western societies. Liver X nuclear receptors (LXRs) regulate the expression of the adenosine triphosphate-binding cassette (ABC) transporters, including adenosine triphosphate-binding cassette transporter A1 (ABCA1) and adenosine triphosphate-binding cassette transporter G1 (ABCG1). ABCA1 and ABCG1 facilitate the efflux of cholesterol from macrophages and regulate high-density lipoprotein (HDL) biogenesis. Increasing evidence supports the role of microRNA (miRNAs) in regulating cholesterol metabolism through ABC transporters.
  
  
  OBJECTIVE
  We aimed to identify novel miRNAs that regulate cholesterol metabolism in macrophages stimulated with LXR agonists.
  
  
  RESULTS
  To map the miRNA expression signature of macrophages stimulated with LXR agonists, we performed an miRNA profiling microarray analysis in primary mouse peritoneal macrophages stimulated with LXR ligands. We report that LXR ligands increase miR-144 expression in macrophages and mouse livers. Overexpression of miR-144 reduces ABCA1 expression and attenuates cholesterol efflux to apolipoproteinA1 in macrophages. Delivery of miR-144 oligonucleotides to mice attenuates ABCA1 expression in the liver, reducing HDL levels. Conversely, silencing of miR-144 in mice increases the expression of ABCA1 and plasma HDL levels. Thus, miR-144 seems to regulate both macrophage cholesterol efflux and HDL biogenesis in the liver.
  
  
  CONCLUSIONS
  miR-144 regulates cholesterol metabolism via suppressing ABCA1 expression and modulation of miRNAs may represent a potential therapeutical intervention for treating dyslipidemia and atherosclerotic vascular disease.
authors.affiliation: Leon H. Charney Division of Cardiology, Departments of Medicine and Cell Biology, New York University School of Medicine, New York, New York, USA.
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Ramírez
authors.forename: Noemi
authors.initials: N
authors.lastname: Rotllan
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Vlassov
authors.forename: Alberto
authors.initials: A
authors.lastname: Dávalos
authors.forename: Mu
authors.initials: M
authors.lastname: Li
authors.forename: Leigh
authors.initials: L
authors.lastname: Goedeke
authors.forename: Juan F
authors.initials: JF
authors.lastname: Aranda
authors.forename: Daniel
authors.initials: D
authors.lastname: Cirera-Salinas
authors.forename: Elisa
authors.initials: E
authors.lastname: Araldi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Salerno
authors.forename: Amarylis
authors.initials: A
authors.lastname: Wanschel
authors.forename: Jiri
authors.initials: J
authors.lastname: Zavadil
authors.forename: Antonio
authors.initials: A
authors.lastname: Castrillo
authors.forename: Jungsu
authors.initials: J
authors.lastname: Kim
authors.forename: Yajaira
authors.initials: Y
authors.lastname: Suárez
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Hernando
mesh_terms: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D016632:Apolipoprotein A-I / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D008076:Cholesterol, HDL / Q000097:blood*; D059305:Diet, High-Fat; D020869:Gene Expression Profiling / Q000379:methods; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D006845:Hydrocarbons, Fluorinated / Q000494:pharmacology; D000071518:Liver X Receptors; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009841:Oligonucleotides / Q000378:metabolism; D057093:Orphan Nuclear Receptors / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
chemical_list: D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D006845:Hydrocarbons, Fluorinated; D000071518:Liver X Receptors; D035683:MicroRNAs; D009841:Oligonucleotides; D057093:Orphan Nuclear Receptors; D013449:Sulfonamides; C577836:ABCA1 protein, human; C505693:APOA1 protein, human; C554293:MIRN144 microRNA, human; C551064:MIRN144 microRNA, mouse; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
keywords: ABCA1; cardiovascular research; cholesterol efflux; cholesterol homeostatis; high-density lipoprotein; lipids and lipoprotein metabolism; microRNAs