140th Edition-The Lipid Lowdown
March 11, 2016
New Sterols linked to Atherosclerosis
The proatherogenic properties of the cholesterol 5,6-secosterols (atheronal-A and atheronal-B), recently discovered in atherosclerotic arteries, have been investigated in terms of their effects on monocyte/macrophage function. A fluorescent analogue of atheronal-B, when cultured in either aqueous buffer or in media containing fetal calf serum, is rapidly taken-up into cultured macrophage cells and accumulates at perinuclear sites………… When complexed with LDL , atheronal-A (but not atheronal-B) induces a dose-dependent upregulation of the cell-surface adhesion molecule endothelial (E)-selectin on vascular endothelial cells. LDL complexed atheronal-B but not atheronal-A induces cultured human monocytes (THP-1) to differentiate into macrophage cell lineage. When these in vitro data are taken together with the already known effects of cholesterol 5,6-secosterols on foam cell formation and macrophage cytotoxicity, the atheronals possess biological effects that if translated to an in vivo setting could lead to the recruitment, entrapment, dysfunction, and ultimate destruction of macrophages, with the major leukocyte player in inflammatory artery disease. As such, the atheronal molecules may be a new association, in the already complex inter-relationship, between inflammation, cholesterol oxidation, the tissue macrophage, and atherosclerosis.
Takeuchi, C., R. Galve, J. Nieva, D.P. Witter, A.D. Wentworth, R.P. Troseth, R.A. Lerner, and P. Wentworth Jr. (2006). Proatherogenic effects of the cholesterol ozonolysis products, atheronal-A and atheronal-B. Biochemistry 45:7162-70.
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