title: Truths and controversies concerning the role of miRNAs in atherosclerosis and lipid metabolism.
abstract: Better tools are sorely needed for both the prevention and treatment of cardiovascular diseases, which account for more than one-third of the deaths in Western countries. MicroRNAs typically regulate the expression of several mRNAs involved in the same biological process. Therapeutic manipulation of miRNAs could restore the expression of multiple players within the same physiologic pathway, and ideally offer better curative outcomes than conventional approaches that target only one single player within the pathway. This review summarizes available studies on the prospective value of targeting miRNAs to prevent dyslipidemia and atherogenesis.
  
  
  
  Silencing the expression of miRNAs that target key genes involved in lipoprotein metabolism in vivo with antisense oligonucleotides results in the expected de-repression of target mRNAs in liver and atherosclerotic plaques. However, the consequences of long-term antimiRNA treatment on both circulating lipoproteins and athero-protection are yet to be established.
  
  
  
  A number of studies have demonstrated the efficacy of miRNA mimics and inhibitors as novel therapeutic tools for treating dyslipidemia and cardiovascular diseases. Nevertheless, concerns over unanticipated side-effects related to de-repression of additional targets should not be overlooked for miRNA-based therapies.
authors.affiliation: aEdward A. Doisy Department of Biochemistry and Molecular Biology, Center for Cardiovascular Research, and Liver Center, Saint Louis University, Saint Louis, Missouri bVascular Biology and Therapeutics Program, Integrative Cell Signaling and Neurobiology of Metabolism Program, Section of Comparative Medicine, and Department of Pathology, Yale University School of Medicine, New Haven, Connecticut, USA.
authors.forename: Ángel
authors.initials: Á
authors.lastname: Baldán
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Hernando
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism*; D001692:Biological Transport / Q000235:genetics; D002784:Cholesterol / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D002784:Cholesterol