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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/12301

Proatherogenic Effects of the Cholesterol Ozonolysis Products, Atheronal-A and Atheronal-B

AutorTakeuchi, Cindy; Galvé, Roger; Nieva, Jorgé; Witter, Daniel P.; Wentworth, Anita D.; Troseth, Ryan P.; Ryan P, Richard A.; Wentworth, Paul Jr.
Palabras claveProatherogenic properties
Atherosclerotic arteries
Monocyte/macrophage function
Cholesterol oxidation
Tissue macrophage
Fecha de publicación17-may-2006
EditorAmerican Chemical Society
CitaciónBiochemistry 45(23): 7162-7170 (2006)
ResumenThe 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 (1) (50 μM), when cultured in either aqueous buffer (PBS) or in media containing fetal calf serum (10%), is rapidly taken-up into cultured macrophage (J774.1 or RAW 264.7) cells and accumulates at perinuclear sites (within 1 h). Co-incubation of macrophage cells (J774.1) with atheronal-A (25 μM) and atheronal-B (25 μM) when complexed with low-density lipoprotein (LDL) (100 μg/mL) leads to a significant upregulation of scavenger receptor class A (3-fold increase relative to LDL alone, p < 0.05) but not CD36, showing that cultured macrophages respond to LDL-complexed atheronals in a manner highly analogous to acetylated LDL rather than oxidized LDL. Both atheronal-A and atheronal-B in solution exhibit a dose-dependent (0−25 μM) induction of chemotaxis of cultured macrophages (p < 0.001). When complexed with LDL (100 μg/mL), atheronal-A (but not atheronal-B) induces a dose-dependent (0−25 μM, p < 0.05) upregulation of the cell-surface adhesion molecule endothelial (E)-selectin on vascular endothelial cells (HUVECs). LDL (100 μg/mL) complexed atheronal-B (25 μM) 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.
Descripción9 pages, 6 figures.
Versión del editorhttp://dx.doi.org/10.1021/bi0604330
ISSN0006-2960 (Print)
1520-4995 (Online)
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