Original ArticleNF-κB inhibitors that prevent foam cell formation and atherosclerotic plaque accumulation
Graphical Abstract
Fullerene derivatives are powerful anti-oxidants capable of significantly reducing the incidence and burden of inflammatory disorders. In the current study we show that fullerene derivatives reduce atherosclerosis of aortic arches of mice as well as a general protective effect when challenged with high fat diets. Taken together, these results are a significant step toward fullerene based therapies for inflammatory diseases.
Section snippets
Fullerene derivatives
A panel of approximately 30 anti-inflammatory FDs9 were initially tested for their ability to inhibit foam cell formation in vitro. From this initial screen both amphiphilic liposomal malonylfullerene (ALM) and tris-malonate fullerene (C3) were chosen for further analysis. The FDs were bought from Luna Innovations and their formulation is described elsewhere.12, 17
Generation of monocyte-derived macrophage foam cells
Low-density lipoproteins from human plasma were oxidized as previously described to produce ox-LDL.18 To obtain macrophage-derived
Fullerene derivatives
The size distribution profile of ALM and C3 was 0.251 μm and 0.117 μm, respectively while the zeta potentials were −59.02 mV and −95.50 mV, suggesting stability of FD in solution. The size distribution and zeta potential did not significantly change after vigorous vortexing or sonication. Nanosight nanoparticle tracking of ALM and C3 revealed a mean particle size of 0.142 μm for ALM and 0.082 μm for C3. The smaller mean size from the Nanosight is a result of the individualized nature of particle size
Discussion
The aim of our study was to determine if FD could prevent the development of atherosclerosis based on the observation that certain FDs could attenuate other chronic inflammatory diseases.11, 36, 37 After initial testing of several FD, two were chosen for further studies based on their ability to inhibit foam cell formation in vitro. Monocyte U937 cells treated with FD had a significant decrease in total ORO staining under conditions that transform them into foam cells compared to untreated
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Cited by (0)
No conflict of interest.
We acknowledge grants 1R01GM083274-01C and R21 ESO15696-01A and NCBC 2012 BRG1203 to CLK.
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Authors Contributed Equally.