Macrophages Can Decrease the Level of Cholesteryl Ester Hydroperoxides in Low Density Lipoprotein

Abstract

Murine and human macrophages rapidly decreased the level of cholesteryl ester hydroperoxides in low density lipoprotein (LDL) when cultured in media non-permissive for LDL oxidation. This process was proportional to cell number but could not be attributed to the net lipoprotein uptake. Macrophage-mediated loss of lipid hydroperoxides in LDL appears to be metal ionindependent. Degradation of cholesteryl linoleate hydroperoxides was accompanied by accumulation of the corresponding hydroxide as the major product and cholesteryl keto-octadecadienoate as a minor product, although taken together these products could not completely account for the hydroperoxide consumption. Cell-conditioned medium possessed a similar capacity to remove lipid hydroperoxides as seen with cellular monolayers, suggesting that the activity is not an integral component of the cell but is secreted from it. The activity of cell-conditioned medium to lower the level of LDL lipid hydroperoxides is associated with its high molecular weight fraction and is modulated by the availability of free thiol groups. Cell-mediated loss of LDL cholesteryl ester hydroperoxides is facilitated by the presence of ␣-tocopherol in the lipoprotein. Together with our earlier reports on the ability of macrophages to remove peroxides rapidly from oxidized amino acids, peptides, and proteins as well as to clear selectively cholesterol 7-␤-hydroperoxide, results presented in this paper provide evidence of a potential protective activity of the cell against further LDL oxidation by removing reactive peroxide groups in the lipoprotein.

Chromium and Manganese Levels in Biological Samples of Pakistani Myocardial Infarction Patients at Different Stages as Related to Controls

“…A study reported that a reduction in macrophage apoptosis stimulates atherosclerosis [54]. On the other hand, macrophages are reported to have antioxidant and, potentially, antiatherogenic roles [55], indicating that a decrease in number of macrophages would promote atherosclerosis. Manganese is a constituent of the antioxidant enzymes superoxide dismutase and adenylyl cyclase.…”

Elimination of Lipid Peroxide during Hemodialysis

“…As the antioxidative side plasma lecithin:cholesterol acyltransferase (LCAT) and apolipoprotein A-I (apoA-I) were studied. These substances are known to eliminate LOOH [11,12,13,14,15, 21, 22]. From a comprehensive evaluation of these parameters we found that CE-OOH was specifically decreased in relation to apoA-I even under the pro-oxidative conditions of HD which leaded us to conclude HD is antioxidative.…”

“…CE-OOH is nonenzymatically reduced to cholesteryl ester hydroxide (CE-OH) by HDL, apoA-I and A-II [11,12,13]. Macrophages are also reported to decrease CE-OOH [22]. In contrast, apoA-I activates LCAT [21].…”

“…Because hydroxyl radical is also able to oxidize cholesteryl ester to CE-OOH, this result suggests the enhancement of CE-OOH specific elimination system(s). Several studies reported on the LOOH elimination system [11,12,13,14,15, 21, 22]. In plasma, PC-OOH is reduced to phosphatidylcholine hydroxide (PC-OH) enzymatically by plasma glutathione peroxidase (PHGPx) or nonenzymatically by apoA-1 or B-100 [14, 30].…”

Human macrophages limit oxidation products in low density lipoprotein

“…Murine macrophages effectively block LDL oxidation by mechanisms which include metal ion sequestration [4]. Recent studies show that macrophages decrease cholesteryl ester hydroperoxide levels in LDL, an antioxidant action that is proportional to cell number [5,6]. In addition, endothelial cells prevent accumulation of lipid hydroperoxides in LDL [7].…”