A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation Articles uri icon

authors

  • DUIVENVOORDEN, RAPHAËL
  • TANG, JUN
  • CORMODE, DAVID P.
  • MIESZAWSKA, ANETA J.
  • IZQUIERDO GARCÍA, DAVID
  • OZCAN, CANTURK
  • OTTEN, MAARTEN J.
  • ZAIDI, NEEHA
  • LOBATTO, MARK E.
  • VAN RIJS, SARIAN M.
  • PRIEM, BRAM
  • KUAN, EMMA L.
  • MARTEL, CATHERINE
  • HEWING, BERND
  • SAGER, HENDRIK
  • NAHRENDORF, MATTHIAS
  • RANDOLPH, GWENDALYN J.
  • STROES, ERIK S. G.
  • FUSTER, VALENTIN
  • FISHER, EDWARD A.
  • FAYAD, ZAHI A.
  • MULDER, WILLEM J.M.

publication date

  • January 2014

start page

  • 3065

volume

  • 5

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

abstract

  • Inflammation is a key feature of atherosclerosis and a target for therapy. Statins have potent anti-inflammatory properties but these cannot be fully exploited with oral statin therapy due to low systemic bioavailability. Here we present an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle that delivers statins to atherosclerotic plaques. We demonstrate the anti-inflammatory effect of statin-rHDL in vitro and show that this effect is mediated through the inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show that they accumulate in atherosclerotic lesions in which they directly affect plaque macrophages. Finally, we demonstrate that a 3-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a 1-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.

subjects

  • Biology and Biomedicine