NF-B-Dependent Prevention of Atherosclerotic Foam Cell Formation and Ves- Sel Plaque Accumulation by Fullerene-Based Nanomedicines

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dc.contributor.authorAnthony L. Dellinger, BS
dc.contributor.authorZhiguo Zhou, PhD
dc.contributor.authorMarinella Sandros, PhD
dc.contributor.authorAshraf Sawafta, PhD
dc.contributor.authorPatty Elkins, MS
dc.contributor.authorChristopher L. Kepley, PhD
dc.date.accessioned2017-05-03T09:34:53Z
dc.date.available2017-05-03T09:34:53Z
dc.date.issued2012-03-26
dc.description.abstract<p>Fullerenes are carbon spheres that have been shown to have anti-inflammatory properties. The transformation of monocytes into foam cells is an inflammatory process underlying atherosclerotic disease. We hypothesized that fullerene derivatives (FD) could inhibit the monocyte-to-foam cell transformation step involved in atherosclerosis. Fullerene derivatives inhibited the phorbol myristilic acid/oxidized low-density lipoprotein differentiation of monocytic U937 cells into foam cells as determined by lipid staining, cell adhesion, and scanning electron microscopy. Oxidized low density lipoprotein-induced generation of TNF-α, leukocyte integrin Mac-1-driven cell clumping, and CD36 receptor expression were significantly inhibited in FD treated cells com- pared to non-treated cells. For the first time it is shown that FD can dramatically reduce NF-κB expression in the oxidized low-density lipoprotein-dependent transformation of macrophages into foam cells. Apolipoprotein E knockout mice (ApoE -/-) fed a high fat diet (HFD) had dramatic inhibition of plaque formation in the blood vessels when treated with FD compared to non-treated controls. Lastly, no in vitro or in vivo toxic- ity was detected with FD; instead the FD helped reduced liver toxicity associated with the HFD. Thus, FD may be a heretofore unrecognized way to prevent atherosclerotic lesions through the inhibition of foam cell formation.</p>en
dc.description.abstract<p>Fullerenes are carbon spheres that have been shown to have anti-inflammatory properties. The transformation of monocytes into foam cells is an inflammatory process underlying atherosclerotic disease. We hypothesized that fullerene derivatives (FD) could inhibit the monocyte-to-foam cell transformation step involved in atherosclerosis. Fullerene derivatives inhibited the phorbol myristilic acid/oxidized low-density lipoprotein differentiation of monocytic U937 cells into foam cells as determined by lipid staining, cell adhesion, and scanning electron microscopy. Oxidized low density lipoprotein-induced generation of TNF-α, leukocyte integrin Mac-1-driven cell clumping, and CD36 receptor expression were significantly inhibited in FD treated cells com- pared to non-treated cells. For the first time it is shown that FD can dramatically reduce NF-κB expression in the oxidized low-density lipoprotein-dependent transformation of macrophages into foam cells. Apolipoprotein E knockout mice (ApoE -/-) fed a high fat diet (HFD) had dramatic inhibition of plaque formation in the blood vessels when treated with FD compared to non-treated controls. Lastly, no in vitro or in vivo toxic- ity was detected with FD; instead the FD helped reduced liver toxicity associated with the HFD. Thus, FD may be a heretofore unrecognized way to prevent atherosclerotic lesions through the inhibition of foam cell formation.</p>ar
dc.identifier.urihttps://hdl.handle.net/20.500.11888/9070
dc.titleNF-B-Dependent Prevention of Atherosclerotic Foam Cell Formation and Ves- Sel Plaque Accumulation by Fullerene-Based Nanomedicinesen
dc.titleNF-B-Dependent Prevention of Atherosclerotic Foam Cell Formation and Ves- Sel Plaque Accumulation by Fullerene-Based Nanomedicinesar
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The First International Palestinian Conference on Nanotechnology for Advanced Material and Devices