TY - JOUR
T1 - A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation
AU - Duivenvoorden, Raphaël
AU - Tang, Jun
AU - Cormode, David P.
AU - Mieszawska, Aneta J.
AU - Izquierdo-Garcia, David
AU - Ozcan, Canturk
AU - Otten, Maarten J.
AU - Zaidi, Neeha
AU - Lobatto, Mark E.
AU - van Rijs, Sarian M.
AU - Priem, Bram
AU - Kuan, Emma L.
AU - Martel, Catherine
AU - Hewing, Bernd
AU - Sager, Hendrik
AU - Nahrendorf, Matthias
AU - Randolph, Gwendalyn J.
AU - Stroes, Erik S. G.
AU - Fuster, Valentin
AU - Fisher, Edward A.
AU - Fayad, Zahi A.
AU - Mulder, Willem J. M.
PY - 2014
Y1 - 2014
N2 - 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
AB - 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
U2 - https://doi.org/10.1038/ncomms4065
DO - https://doi.org/10.1038/ncomms4065
M3 - Article
C2 - 24445279
SN - 2041-1723
VL - 5
SP - 3065
JO - Nature communications
JF - Nature communications
ER -