Atorvastatin and hormone therapy effects on APOE mRNA expression in hypercholesterolemic postmenopausal women

• Published in: The Journal of steroid biochemistry and molecular biology 2012-02, Vol.128 (3-5), p.139-144
• Main Authors: Issa, Mustafa H., Cerda, Alvaro, Genvigir, Fabiana D.V., Cavalli, Selma A., Bertolami, Marcelo C., Faludi, Andre A., Hirata, Mario H., Hirata, Rosario D.C.
• Format: Article
• Language: English
• Subjects: Aged; Amplified Fragment Length Polymorphism Analysis; Apolipoprotein E (apoE); Apolipoproteins - blood; Apolipoproteins E - genetics; Apolipoproteins E - metabolism; Atorvastatin; Atorvastatin Calcium; Brazil; Cholesterol, LDL - blood; Down-Regulation - drug effects; Drug Therapy, Combination - adverse effects; Estrogen Replacement Therapy - adverse effects; Estrogen Replacement Therapy - methods; Female; Gene expression; Heptanoic Acids - adverse effects; Heptanoic Acids - therapeutic use; Hormone therapy (HT); Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia - blood; Hypercholesterolemia - drug therapy; Hypercholesterolemia - genetics; Hypercholesterolemia - metabolism; Leukocytes, Mononuclear - drug effects; Leukocytes, Mononuclear - metabolism; Liver X Receptors; Menopause; Middle Aged; Orphan Nuclear Receptors - genetics; Orphan Nuclear Receptors - metabolism; Polymorphism, Single Nucleotide; Postmenopause; Pyrroles - adverse effects; Pyrroles - therapeutic use; RNA, Messenger - metabolism; Single nucleotide polymorphism (SNP)
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2011.11.001

► We studied postmenopausal women submitted to atorvastatin and hormone replacement. ► We evaluated effects of treatments and SNPs on modulation of APOE expression. ► APOE and LXRA expression are positively correlated before and after treatments. ► APOE expression on mononuclear cells is down-regulated by atorvastatin treatment. ► APOE down-regulation by atorvastatin is influenced by APOE genotypes. Menopause is associated with changes in lipid levels resulting in increased risk of atherosclerosis and cardiovascular events. Hormone therapy (HT) and atorvastatin have been used to improve lipid profile in postmenopausal women. Effects of HT, atorvastatin and APOE polymorphisms on serum lipids and APOE and LXRA expression were evaluated in 87 hypercholesterolemic postmenopausal women, randomly selected for treatment with atorvastatin (AT, n=17), estrogen or estrogen plus progestagen (HT, n=34) and estrogen or estrogen plus progestagen associated with atorvastatin (HT+AT, n=36). RNA was extracted from peripheral blood mononuclear cells (PBMC) and mRNA expression was measured by TaqMan® PCR. APOE ɛ2/ɛ3/ɛ4 genotyping was performed using PCR-RFLP. Total cholesterol (TC), LDL-c and apoB were reduced after each treatment (p