title: Therapeutic gene targeting approaches for the treatment of dyslipidemias and atherosclerosis.
abstract: OBJECTIVE
  Despite improved therapies, cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Therefore, new therapeutic approaches are still needed. In the gene therapy field, RNA interference (RNAi) and regulation of microRNAs (miRNAs) have gained a lot of attention in addition to traditional overexpression based strategies. Here, recent findings in therapeutic gene silencing and modulation of small RNA expression related to atherogenesis and dyslipidemia are summarized.
  
  
  RESULTS
  Novel gene therapy approaches for the treatment of hyperlipidemia have been addressed. Antisense oligonucleotide and RNAi-based therapies against apolipoprotein B100 and proprotein convertase subtilisin/kexin type 9 have shown already efficacy in preclinical and clinical trials. In addition, several miRNAs dysregulated in atherosclerotic lesions and regulating cholesterol homeostasis have been found, which may represent novel targets for future therapies.
  
  
  CONCLUSIONS
  New therapies for lowering lipid levels are now being tested in clinical trials, and both antisense oligonucleotide and RNAi-based therapies have shown promising results in lowering cholesterol levels. However, the modulation of inflammatory component in atherosclerosis by gene therapy and targeting of the effects to plaques are still difficult challenges.
authors: Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland.
authors: Petri I
authors: PI
authors: Mäkinen
authors: Seppo
authors: S
authors: Ylä-Herttuala
mesh_terms: D050197:Atherosclerosis / Q000235:genetics / Q000628:therapy*; D008076:Cholesterol, HDL / Q000235:genetics / Q000378:metabolism; D008078:Cholesterol, LDL / Q000235:genetics / Q000378:metabolism; D002986:Clinical Trials as Topic; D050171:Dyslipidemias / Q000235:genetics / Q000628:therapy*; D044127:Epigenesis, Genetic; D015316:Genetic Therapy; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D035683:MicroRNAs; D034741:RNA, Small Interfering