A novel lipoprotein (a) lowering drug, D-47, decreases neointima thickening after vascular injury

J Med Invest. 2017;64(1.2):64-67. doi: 10.2152/jmi.64.64.

Abstract

Although Lp(a) have been thought to be a cardiovascular risk factor, it is unclear whether lowering Lp(a) levels reduces the risk of cardiovascular diseases. No pharmacological agents which selectively reduce serum Lp(a) levels, and Lp(a) is present in primate but absent in common laboratory animals such as mice and pigs. In the present study we used transgenic mice of human Lp(a) and tested effect a novel Lp(a) lowering drug D-47 on neointima formation after vascular injury. D-47 successfully decreased plasma levels of Lp(a) and possibly inhibited neointima formation in Lp(a) transgenic mice. The results indicate that we can modulate plasma Lp(a) levels by pharmacologic agents and inhibit atherogenic properties of Lp(a) by reducing plasma levels of Lp(a). J. Med. Invest. 64: 64-67, February, 2017.

MeSH terms

  • Animals
  • Femoral Artery / drug effects
  • Femoral Artery / injuries
  • Femoral Artery / pathology
  • Humans
  • Hydroxybenzoate Ethers / pharmacology*
  • Hypolipidemic Agents / pharmacology*
  • Lipoprotein(a) / antagonists & inhibitors*
  • Lipoprotein(a) / blood
  • Lipoprotein(a) / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Neointima / blood
  • Neointima / drug therapy*
  • Neointima / pathology
  • Polyethylene Glycols / pharmacology
  • Polyvinyls / pharmacology
  • Pyrrolidinones / pharmacology*
  • Recombinant Proteins / blood
  • Recombinant Proteins / genetics
  • Vascular System Injuries / blood
  • Vascular System Injuries / drug therapy*
  • Vascular System Injuries / pathology

Substances

  • 4-(1-(4-tert-butylphenyl)-2-oxopyrrolidine-4-yl)methyloxybenzoic acid
  • Hydroxybenzoate Ethers
  • Hypolipidemic Agents
  • Lipoprotein(a)
  • Polyvinyls
  • Pyrrolidinones
  • Recombinant Proteins
  • polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer
  • Polyethylene Glycols