title: Inhibition of ApoCIII: the next PCSK9?
abstract: OBJECTIVE
  Recent large Mendelian randomization studies associate loss-of-function mutations in apolipoprotein CIII (APOCIII) with low levels of triglycerides and decreased incidence of cardiovascular disease. With ample in-vitro and in-vivo evidence for a role of apoCIII in lipoprotein lipase-mediated triglyceride clearance and remnant removal, it is, thus, an attractive target for the treatment of hypertriglyceridemia and the prevention of cardiovascular disease. This review evaluates the current position of apoCIII in clinical practice and provides a glimpse into the future in terms of treatment options.
  
  
  RESULTS
  Two large Mendelian randomization studies have shown three identical loss-of-function mutations in APOCIII to be linked to favorable lipid profiles and lower incidence of coronary artery disease. A second-generation antisense oligonucleotide, which selectively inhibits apoCIII, was able to decrease serum apoCIII and triglyceride levels in rodents, nonhuman primates and humans.
  
  
  CONCLUSIONS
  The central role of apoCIII in hypertriglyceridemia and cardiovascular disease was further cemented by recent findings and promising intervention data that showed the possibility of using antisense therapy to lower apoCIII and triglyceride levels. Currently, planned phase 3 trials should provide answers in regards to long-term efficacy and safety of this novel therapy.
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Universiteit van Amsterdam, Amsterdam, the Netherlands.
authors.forename: Sophie J
authors.initials: SJ
authors.lastname: Bernelot Moens
authors.forename: Julian C
authors.initials: JC
authors.lastname: van Capelleveen
authors.forename: Erik S G
authors.initials: ES
authors.lastname: Stroes
mesh_terms: D000818:Animals; D053305:Apolipoprotein C-III / Q000037:antagonists & inhibitors* / Q000097:blood / Q000235:genetics; D017326:Clinical Trials, Phase III as Topic; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods; D000882:Haplorhini; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000150:complications / Q000235:genetics / Q000628:therapy*; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000235:genetics* / Q000378:metabolism; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000037:antagonists & inhibitors / Q000235:genetics; D016032:Randomized Controlled Trials as Topic; D012697:Serine Endopeptidases / Q000235:genetics; D014280:Triglycerides / Q000037:antagonists & inhibitors* / Q000097:blood
chemical_list: D053305:Apolipoprotein C-III; D016376:Oligonucleotides, Antisense; D014280:Triglycerides; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases