Duivenvoorden, RaphaëlTang, JunCormode, David P.Mieszawska, Aneta J.Izquierdo-Garcia, DavidOzcan, CanturkOtten, Maarten J.Zaidi, NeehaLobatto, Mark E.van Rijs, Sarian M.Priem, BramKuan, Emma L.Martel, CatherineHewing, BerndSager, Hendrik BNahrendorf, MatthiasRandolph, Gwendalyn J.Stroes, Erik S.G.Fuster, ValentinFisher, Edward A.Fayad, Zahi A.Mulder, Willem J.M.2014-08-132014Duivenvoorden, R., J. Tang, D. P. Cormode, A. J. Mieszawska, D. Izquierdo-Garcia, C. Ozcan, M. J. Otten, et al. 2014. “A Statin-Loaded Reconstituted High-Density Lipoprotein Nanoparticle Inhibits Atherosclerotic Plaque Inflammation.” Nature communications 5 (1): 3065. doi:10.1038/ncomms4065. http://dx.doi.org/10.1038/ncomms4065.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:12717557Inflammation 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 this effect is mediated through inhibition of the mevalonate pathway. We also apply statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and show they accumulate in atherosclerotic lesions where they directly affect plaque macrophages. Finally we demonstrate that a three-month low-dose statin-rHDL treatment regimen inhibits plaque inflammation progression, while a one-week high-dose regimen markedly decreases inflammation in advanced atherosclerotic plaques. Statin-rHDL represents a novel potent atherosclerosis nanotherapy that directly affects plaque inflammation.en-USJournal Article2014-08-1310.1038/ncomms4065