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

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. FisherZahi A. Fayad, Willem J.M. Mulder

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number3065
JournalNature communications
Volume5
DOIs
StatePublished - Jan 1 2014
Externally publishedYes

Fingerprint

lipoproteins
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Atherosclerotic Plaques
HDL Lipoproteins
Nanoparticles
arteriosclerosis
Inflammation
nanoparticles
Atherosclerosis
therapy
knockout mice
bioavailability
dosage
macrophages
Anti-Inflammatory Agents
progressions
lesions
Mevalonic Acid
Macrophages
vehicles

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Duivenvoorden, R., Tang, J., Cormode, D. P., Mieszawska, A. J., Izquierdo-Garcia, D., Ozcan, C., ... Mulder, W. J. M. (2014). A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation. Nature communications, 5, [3065]. https://doi.org/10.1038/ncomms4065

A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation. / Duivenvoorden, Raphaël; Tang, Jun; Cormode, David P.; Mieszawska, Aneta J.; Izquierdo-Garcia, 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.

In: Nature communications, Vol. 5, 3065, 01.01.2014.

Research output: Contribution to journalArticle

Duivenvoorden, R, Tang, J, Cormode, DP, Mieszawska, AJ, Izquierdo-Garcia, D, Ozcan, C, Otten, MJ, Zaidi, N, Lobatto, ME, Van Rijs, SM, Priem, B, Kuan, EL, Martel, C, Hewing, B, Sager, H, Nahrendorf, M, Randolph, GJ, Stroes, ESG, Fuster, V, Fisher, EA, Fayad, ZA & Mulder, WJM 2014, 'A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation', Nature communications, vol. 5, 3065. https://doi.org/10.1038/ncomms4065
Duivenvoorden, Raphaël ; Tang, Jun ; Cormode, David P. ; Mieszawska, Aneta J. ; Izquierdo-Garcia, 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. / A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation. In: Nature communications. 2014 ; Vol. 5.
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