NF-κB inhibitors that prevent foam cell formation and atherosclerotic plaque accumulation.

Abstract

The transformation of monocyte-derived macrophages into lipid-laden foam cells is one inflammatory process underlying atherosclerotic disease. Previous studies have demonstrated that fullerene derivatives (FDs) have inflammation-blunting properties. Thus, it was hypothesized that FD could inhibit the transformation process underlying foam cell formation. Fullerene derivatives inhibited the phorbol myristic acid/oxidized low-density lipoprotein-induced differentiation of macrophages into foam cells as determined by lipid staining and morphology.Lipoprotein-induced generation of TNF-α, C5a-induced MC activation, ICAM-1 driven adhesion, and CD36 expression were significantly inhibited in FD treated cells compared to non-treated cells. Inhibition appeared to be mediated through the NF-κB pathway as FD reduced expression of NF-κB and atherosclerosis-associated genes. Compared to controls, FD dramatically inhibited plaque formation in arteries of apolipoprotein E null mice. Thus, FD may be an unrecognized therapy to prevent atherosclerotic lesions via inhibition of foam cell formation and MC stabilization.

• Authors: Jesse D Plotkin, Michael G Elias, Anthony L Dellinger, Christopher L Kepley
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 13 Issue 6 Pg. 2037-2048 (Aug 2017) ISSN: 1549-9642 [Electronic] United States
• PMID: 28457935 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Fullerenes
• NF-kappa B

Topics

• Animals
• Cells, Cultured
• Foam Cells (drug effects, metabolism, pathology)
• Fullerenes (pharmacology)
• Humans
• Male
• Mast Cells (drug effects, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout, ApoE
• NF-kappa B (antagonists & inhibitors)
• Plaque, Atherosclerotic (metabolism, pathology, prevention & control)
• U937 Cells