Novel Therapeutic Targets for Managing Dyslipidemia

Trends Pharmacol Sci. 2018 Aug;39(8):733-747. doi: 10.1016/j.tips.2018.06.001. Epub 2018 Jun 30.

Abstract

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality in developed nations. Therapeutic modulation of dyslipidemia by inhibiting 3'-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase is standard practice throughout the world. However, based on findings from Mendelian studies and genetic sequencing in prospective longitudinal cohorts from around the world, novel therapeutic targets regulating lipid and lipoprotein metabolism, such as apoprotein C3, angiopoietin-like proteins 3 and 4, and lipoprotein(a), have been identified. These targets may provide additional avenues to prevent and treat atherosclerotic disease. We therefore review these novel molecular targets by addressing available Mendelian and observational data, therapeutic agents in development, and early outcomes results.

Keywords: ATP citrate lyase; angiopoietin-like proteins 3 and 4; apoprotein C3; lipoprotein(a); lysosomal acid lipase; proprotein convertase subtilisin/kexin type 9.

Publication types

  • Review

MeSH terms

  • Acyl Coenzyme A / antagonists & inhibitors
  • Acyl Coenzyme A / genetics
  • Angiopoietin-like Proteins / genetics
  • Angiopoietin-like Proteins / metabolism
  • Animals
  • Apolipoproteins C / genetics
  • Apolipoproteins C / metabolism
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism
  • Dyslipidemias / drug therapy*
  • Dyslipidemias / genetics
  • Dyslipidemias / metabolism
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Lipid Metabolism / drug effects
  • Molecular Targeted Therapy
  • Prospective Studies

Substances

  • Acyl Coenzyme A
  • Angiopoietin-like Proteins
  • Apolipoproteins C
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • 3-hydroxy-3-methylglutaryl-coenzyme A