A statin-loaded reconstituted high-density lipoprotein nanoparticle inhibits atherosclerotic plaque inflammation
| Autor: | Emma L. Kuan, Jun Tang, Mark E. Lobatto, Matthias Nahrendorf, Valentin Fuster, Willem J. M. Mulder, Aneta J. Mieszawska, Erik S.G. Stroes, Catherine Martel, Hendrik B. Sager, David Izquierdo-Garcia, Bernd Hewing, Raphaël Duivenvoorden, David P. Cormode, Canturk Ozcan, Maarten J. Otten, Zahi A. Fayad, Sarian M. van Rijs, Gwendalyn J. Randolph, Edward A. Fisher, Neeha Zaidi, Bram Priem |
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| Přispěvatelé: | Vascular Medicine, Radiology and Nuclear Medicine, ACS - Amsterdam Cardiovascular Sciences, Experimental Vascular Medicine |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Statin Apolipoprotein B medicine.drug_class General Physics and Astronomy Inflammation General Biochemistry Genetics and Molecular Biology Article chemistry.chemical_compound Mice High-density lipoprotein Apolipoproteins E In vivo medicine Animals cardiovascular diseases Mice Knockout Multidisciplinary biology Dose-Response Relationship Drug business.industry nutritional and metabolic diseases General Chemistry In vitro Plaque Atherosclerotic 3. Good health Disease Models Animal Treatment Outcome chemistry Immunology Cancer research biology.protein Nanoparticles Administration Intravenous lipids (amino acids peptides and proteins) Mevalonate pathway medicine.symptom Hydroxymethylglutaryl-CoA Reductase Inhibitors business Lipoproteins HDL Lipoprotein |
| Zdroj: | Nature communications Nature communications, 5. Nature Publishing Group |
| DOI: | 10.1038/ncomms4065 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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