title: Anti-miR-33 therapy does not alter the progression of atherosclerosis in low-density lipoprotein receptor-deficient mice.
abstract: OBJECTIVE
  To determine the efficacy of long-term anti-miR-33 therapy on the progression of atherosclerosis in high-fat, high-cholesterol-fed Ldlr(-/-) mice.
  
  
  RESULTS
  Ldlr(-/-) mice received saline, or control or anti-miR-33 oligonucleotides once a week for 14 weeks. The treatment was effective, as measured by reduced levels of hepatic miR-33 and increased hepatic expression of miR-33 targets. Analysis of plasma samples revealed an initial elevation in high-density lipoprotein cholesterol after 2 weeks of treatment that was not sustained by the end of the experiment. Additionally, we found a significant increase in circulating triglycerides in anti-miR-33-treated mice, compared with controls. Finally, examination of atheromata revealed no significant changes in the size or composition of lesions between the 3 groups.
  
  
  CONCLUSIONS
  Prolonged silencing of miR-33 fails to maintain elevated plasma high-density lipoprotein cholesterol and does not prevent the progression of atherosclerosis in Ldlr(-/-) mice.
authors.affiliation: Edward A. Doisy Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA.
authors.forename: Tyler J
authors.initials: TJ
authors.lastname: Marquart
authors.forename: Judy
authors.initials: J
authors.lastname: Wu
authors.forename: Aldons J
authors.initials: AJ
authors.lastname: Lusis
authors.forename: Ángel
authors.initials: Á
authors.lastname: Baldán
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D015415:Biomarkers / Q000097:blood; D002791:Cholesterol, Dietary / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000378:metabolism*; D011973:Receptors, LDL / Q000172:deficiency* / Q000235:genetics; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D015415:Biomarkers; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D035683:MicroRNAs; C550417:Mirn33 microRNA, mouse; D016376:Oligonucleotides, Antisense; D011973:Receptors, LDL; D014280:Triglycerides