2015
DOI: 10.1126/sciadv.1400223
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Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation

Abstract: Nanoparticle-based delivery of simvastatin inhibits plaque macrophage proliferation in apolipoprotein E–deficient mice.

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Cited by 195 publications
(168 citation statements)
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“…This indicates that preventing cell cycle progression interferes with monocyte-derived cell polarization and inhibits their suppressive function. To evaluate the effects of S-HDL in vivo, we next incorporated simvastatin at a concentration of 60mg/kg in S-HDL nanoparticles to inhibit macrophages proliferation (26). A conservative S-HDL regimen that included three i.v.…”
Section: Resultsmentioning
confidence: 99%
“…This indicates that preventing cell cycle progression interferes with monocyte-derived cell polarization and inhibits their suppressive function. To evaluate the effects of S-HDL in vivo, we next incorporated simvastatin at a concentration of 60mg/kg in S-HDL nanoparticles to inhibit macrophages proliferation (26). A conservative S-HDL regimen that included three i.v.…”
Section: Resultsmentioning
confidence: 99%
“…Previous studies indicate that the size, phospholipid composition, ratio of phospholipid to apolipoprotein A-1 (APOA1), or the inclusion of payloads can affect HDL-mimicking nanoparticles' in vivo performance (12)(13)(14). In our current study, we created a library containing HDL-mimicking nanoparticles that differ in size, shape, composition, and payload, all of which have been reported to affect nanoparticles' A C Diameter (nm) 400 200 80 40 0 NP1 NP2 NP3 NP4 NP5 NP6 NP7 NP8 NP9 NP10 NP11 NP12 NP13 NP14 NP15 NP16 NP17 50 0 100 150 NP1 NP2 NP3 NP4 NP5 NP6 NP7 NP8 NP9 NP10 NP11 NP12 NP13 NP14 NP15 NP16 NP17 D B NP1 NP2 NP3 NP4 NP5 NP6 NP7 NP8 NP9 NP10 NP11 NP12 NP13 NP14 NP15 NP16 NP17 + GW3965 Nanoparticle in vivo immune cell screen Improving drug therapeutic index In the in vivo immune cell screen study (left), we first created a combinatorial nanoparticle library and then evaluated the library in atherosclerotic Apoe −/− mice by using blood half-life determination, NIRF, and flow cytometry.…”
Section: Resultsmentioning
confidence: 99%
“…CD45 + CD11b + F4/80 + macrophages were isolated using the BD FACS Aria IIu SORP from pre-transplant baseline and grafted arches from WT recipient mice (regression) that were removed after perfusion of cold PBS and enzymatic digestion as described in ref. 44. Cell surface markers were labeled with the following antibodies: CD45 PerCpCy5.5 (BioLegend, catalog 103132), CD11b AF700 (BioLegend, catalog 101222), and F4/80 PeCy7 (BioLegend, catalog 123114).…”
Section: Methodsmentioning
confidence: 99%