A Statin-Loaded Reconstituted High-Density Lipoprotein Nanoparticle Inhibits Atherosclerotic Plaque Inflammation

نویسندگان

  • Raphaël Duivenvoorden
  • Jun Tang
  • David P. Cormode
  • Aneta J. Mieszawska
  • David Izquierdo-Garcia
  • Canturk Ozcan
  • Maarten J. Otten
  • Neeha Zaidi
  • Mark E. Lobatto
  • Sarian M. van Rijs
  • Bram Priem
  • Emma L. Kuan
  • Catherine Martel
  • Bernd Hewing
  • Hendrik Sager
  • Matthias Nahrendorf
  • Gwendalyn J. Randolph
  • Erik S.G. Stroes
  • Valentin Fuster
  • Edward A. Fisher
  • Zahi A. Fayad
  • Willem J.M. Mulder
چکیده

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.

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عنوان ژورنال:

دوره 5  شماره 

صفحات  -

تاریخ انتشار 2014