title: Therapeutic silencing of microRNA-33 inhibits the progression of atherosclerosis in Ldlr-/- mice--brief report.
abstract: OBJECTIVE
  To study the efficacy of anti-miRNA-33 therapy on the progression of atherosclerosis.
  
  
  RESULTS
  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.
authors.affiliation: Department of Medicine, Leon H Charney Division of Cardiology and Cell Biology and the Marc and Ruti Bell Vascular Biology and Disease Program, New York University School of Medicine, New York, NY, USA.
authors.forename: Noemi
authors.initials: N
authors.lastname: Rotllan
authors.forename: Cristina M
authors.initials: CM
authors.lastname: Ramírez
authors.forename: Binod
authors.initials: B
authors.lastname: Aryal
authors.forename: Christine C
authors.initials: CC
authors.lastname: Esau
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Hernando
mesh_terms: D000821:Animal Feed; D000818:Animals; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D008076:Cholesterol, HDL / Q000097:blood; D018450:Disease Progression; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods*; D007279:Injections, Subcutaneous; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics*; D009841:Oligonucleotides / Q000235:genetics / Q000494:pharmacology; D011973:Receptors, LDL / Q000235:genetics*
chemical_list: D008076:Cholesterol, HDL; D035683:MicroRNAs; C550417:Mirn33 microRNA, mouse; D009841:Oligonucleotides; D011973:Receptors, LDL
keywords: ABCA1 protein; atherosclerosis; cholesterol, HDL; macrophages; miR-33