Atorvastatin and hormone therapy influence expression of ABCA1, APOA1 and SCARB1 in mononuclear cells from hypercholesterolemic postmenopausal women

• Published in: The Journal of steroid biochemistry and molecular biology 2013-11, Vol.138, p.403-409
• Main Authors: Cerda, Alvaro, Issa, Mustafa H., Genvigir, Fabiana D.V., Rohde, Cintia B., Cavalli, Selma A., Bertolami, Marcelo C., Faludi, Andre A., Hirata, Mario H., Hirata, Rosario D.C.
• Format: Article
• Language: English
• Subjects: Anticholesteremic Agents - administration & dosage; Anticholesteremic Agents - therapeutic use; Apolipoprotein A-I - genetics; Apolipoprotein A-I - metabolism; Atorvastatin Calcium; ATP Binding Cassette Transporter 1 - genetics; ATP Binding Cassette Transporter 1 - metabolism; Cells, Cultured; Estradiol - therapeutic use; Female; Heptanoic Acids - administration & dosage; Heptanoic Acids - therapeutic use; Heterocyclic Compounds - therapeutic use; Hormone therapy; Humans; Hypercholesterolemia; Hypercholesterolemia - drug therapy; Hypercholesterolemia - genetics; Hypercholesterolemia - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Menopause; Middle Aged; Postmenopause; Pyrroles - administration & dosage; Pyrroles - therapeutic use; Reverse cholesterol transport (RCT); Scavenger Receptors, Class B - genetics; Scavenger Receptors, Class B - metabolism; Statins; Transcriptome
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2013.08.017

•We studied RCT related genes in postmenopausal women under atorvastatin and hormone replacement.•Hormone therapy plus atorvastatin association treatment had a better impact in improving the lipid profile.•ABCA1 expression in PBMC was down-regulated by atorvastatin, hormone therapy and their combination.•Atorvastatin reduced APOA1 expression whereas hormone therapy reduced SCARB1 expression.•LXRA was correlated with ABCA1, APOA1 and SCARB1 RNAm values before and after treatments. 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. 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). 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. 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.