Therapeutic silencing of microRNA-33 inhibits the progression of atherosclerosis in Ldlr-/- mice--brief report.
Arterioscler Thromb Vasc Biol
; 33(8): 1973-7, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23702658
ABSTRACT
OBJECTIVE:
To study the efficacy of anti-miRNA-33 therapy on the progression of atherosclerosis. APPROACH ANDRESULTS:
Ldlr(-/-) mice were injected subcutaneously with PBS, control, or anti-miR-33 oligonucleotides weekly and fed a Western diet for 12 weeks. At the end of treatment, the expression of miR-33 target genes was increased in the liver and aorta, demonstrating effective inhibition of miR-33 function. Interestingly, plasma high-density lipoprotein (HDL)-cholesterol was significantly increased in anti-miR-33-treated mice but only when they were fed a chow diet. However, HDL isolated from anti-miR-33-treated mice showed an increase cholesterol efflux capacity compared with HDL isolated from nontargeting oligonucleotide-treated mice. Analysis of atherosclerosis revealed a significant reduction of plaque size and macrophage content in mice receiving anti-miR-33. In contrast, no differences in collagen content and necrotic areas were observed among the 3 groups.CONCLUSIONS:
Long-term anti-miR-33 therapy significantly reduces the progression of atherosclerosis and improves HDL functionality. The antiatherogenic effect is independent of plasma HDL-cholesterol levels.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de LDL
/
Terapia Genética
/
MicroRNAs
/
Aterosclerose
Limite:
Animals
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article