title: Atorvastatin and hormone therapy influence expression of ABCA1, APOA1 and SCARB1 in mononuclear cells from hypercholesterolemic postmenopausal women.
abstract: BACKGROUND
  Reverse cholesterol transport (RCT) has been inversely related to atherosclerosis and cardiovascular risk. The influence of menopause in the RCT process is poorly understood and the effects of cholesterol-lowering interventions, including statins and hormone therapy (HT), on genes controlling the RCT in postmenopausal women are also unknown.
  
  
  METHODS
  The effects on serum lipids and expression profile of genes involved in RCT - APOA1, ABCA1, ABCG1, SCARB1 and LXRA - were evaluated by TaqMan(®) quantitative PCR in peripheral blood mononuclear cells (PBMC) from 87 postmenopausal hypercholesterolemic women treated with atorvastatin (AT, n=17), estrogen or estrogen plus progestin (HT, n=34) and estrogen or estrogen plus progestin associated with atorvastatin (HT+AT, n=36).
  
  
  RESULTS
  Atorvastatin and HT treatments reduced the mRNA levels of APOA1 and SCARB1, respectively, whereas ABCA1 expression was reduced after all treatments. Although the expression of LXRA, an important transcription factor controlling the expression of genes involved in RCT, was not modified after any treatment, it was correlated with ABCA1, APOA1 and SCARB1 RNAm values before and after treatments, however no correlation with ABCG1 was observed. In a linear regression analysis, HT was related to an increase in apoAI levels after treatment when compared to atorvastatin and, moreover, higher SCARB1 and ABCA1 basal expression were also associated with decreased apoAI levels after treatments.
  
  
  CONCLUSIONS
  ABCA1 mRNA levels are decreased by atorvastatin and HT, however these treatments have a differential effect on APOA1 and SCARB1 expression in PBMC from postmenopausal women. Basal ABCA1 and SCARB1 expression profile could be helpful markers in predicting the effect of atorvastatin and HT on RCT, according to the changes in apoAI levels in this sample population.
authors.affiliation: School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo, Brazil. Electronic address: alvarocerda@usp.br.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Cerda
authors.forename: Mustafa H
authors.initials: MH
authors.lastname: Issa
authors.forename: Fabiana D V
authors.initials: FD
authors.lastname: Genvigir
authors.forename: Cintia B
authors.initials: CB
authors.lastname: Rohde
authors.forename: Selma A
authors.initials: SA
authors.lastname: Cavalli
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Bertolami
authors.forename: Andre A
authors.initials: AA
authors.lastname: Faludi
authors.forename: Mario H
authors.initials: MH
authors.lastname: Hirata
authors.forename: Rosario D C
authors.initials: RD
authors.lastname: Hirata
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism*; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism*; D000069059:Atorvastatin; D002478:Cells, Cultured; D004958:Estradiol / Q000627:therapeutic use; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006571:Heterocyclic Compounds / Q000627:therapeutic use; D006801:Humans; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D017698:Postmenopause; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D051122:Scavenger Receptors, Class B / Q000235:genetics / Q000378:metabolism*; D059467:Transcriptome
chemical_list: C529856:(2-(4,7-biscarboxymethyl(1,4,7)triazacyclonona-1-yl-ethyl)carbonylmethylamino)acetic acid; C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D006538:Heptanoic Acids; D006571:Heterocyclic Compounds; D011758:Pyrroles; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D004958:Estradiol; D000069059:Atorvastatin
keywords: Hormone therapy; Hypercholesterolemia; Menopause; Reverse cholesterol transport (RCT); Statins