Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cellular lipoxygenases have been implicated in foam cell formation during the early stages of atherogenesis. We studied the interaction of lipoxygenases of different positional specificities with human lipoproteins and found that the arachidonate 15-lipoxygenases of rabbit and humans and the arachidonate 12-lipoxygenase of porcine leukocytes oxygenate lipoproteins as indicated by the formation of oxygenated lipids and changes in electrophoretic mobility of low density lipoprotein. The arachidonate 12-lipoxygenase of human platelets, the recombinant arachidonate 5-lipoxygenase of human leukocyte, and the soybean lipoxygenase I were less effective in oxidizing human LDL. As a major oxygenation product, esterified 13S-hydro(pero)xy-9Z,11E-octadecadienoic acid was identified for both the rabbit reticulocyte 15- and the porcine leukocyte 12-lipoxygenase. In addition, esterified 15S-hydro(pero)xy-5,8,11,13(Z,Z,Z,E)-eicosatetraenoic acid (for the rabbit 15-lipoxygenase) and 12S-hydro(pero)xy-5,8,10,14(Z,Z,E,Z)-eicosatetraenoic acid (for the porcine 12-lipoxygenase) as well as small amounts of racemic 9-hydro(pero)xy-10,12-octadecadienoic acid isomers were detected. More than 90% of the oxygenated polyenoic fatty acids were found in the ester lipid fraction, particularly in the cholesteryl esters and in various phospholipid classes (phosphatidylcholine and phosphatidylethanolamine). The possible biological significance of lipoxygenase-induced oxidative modification of lipoproteins in the pathogenesis of atherosclerosis is discussed.
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PMID:Oxidative modification of human lipoproteins by lipoxygenases of different positional specificities. 785 52

Oxidative modification converts low-density lipoprotein (LDL) into its atherogenic form and appears to be a necessary precondition for LDL uptake by macrophages during foam cell formation. Cellular lipoxygenases have been implicated in this process. We studied the interaction of purified mammalian lipoxygenases with human LDL in vitro and found that the arachidonate 15-lipoxygenases of rabbit and man are capable of oxygenating lipoproteins as indicated by oxygen uptake and by the formation of thiobarbituric-acid-reactive substances. Furthermore, oxygenated polyenoic fatty acids, such as 13-hydro(pero)xy-9Z,11E-octadecadienoic acid and 15-hydro(pero)xy-5,8,11,13(Z,Z,Z,E)-eicosatetraenoic acid were detected in the lipid compartment of various lipoproteins classes after lipoxygenase treatment. More than 90% of the oxygenated polyenoic fatty acids were found in the ester-lipid fraction, particularly in the cholesterol esters, whereas only small amounts of free hydro(pero)xy polyenoic fatty acids were detected. Lipoxygenase-catalyzed oxygenation of LDL is not restricted to the lipid compartment but also leads to a cooxidative modification of the apoproteins as indicated by changes in the electrophoretic mobility and by the formation of carbonyl derivatives of amino acid side chains. The possible biological significance of lipoxygenase-induced oxidative modification of lipoproteins in the pathogenesis of atherosclerosis is discussed.
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PMID:Oxygenation of lipoproteins by mammalian lipoxygenases. 847 99

Oxidative modification of low density lipoprotein has been suggested as patho-physiologically relevant process in atherogenesis and the lipid peroxidizing enzyme 15-lipoxygenase may be involved. For experimental evidence on the in vivo action of this enzyme in the time course of plaque formation we analyzed the lipid extracts of lesional areas representing various stages of human atherogenesis for the occurrence of specific 15-lipoxygenase products. In advanced human lesions the degree of oxygenation of the lesion lipids measured as hydroxy linoleic acid/linoleic acid ratio varied between 0.2 and 3.2%. Here an unspecific pattern of oxygenated lipids that did not differ from the pattern formed during copper-catalyzed LDL oxidation was detected. In both cases an enantiomer ratio (S/R-ratio) of 13-hydroxy-9Z,11E-octadecadienoic acid (13-HODE) of approximately 1:1 was found. In young human lesions which were obtained from the collection of the pathological determinants of atherosclerosis in youth (PDAY) program the hydroxy linoleic acid/linoleic acid ratio was much smaller (variation between 0.05 and 0.6%), and a significant share of specific 15-lipoxygenase products was detected (S/R-ratio of 13-hydroxy linoleic acid of 54 +/- 3.1/46 +/- 3.1 [mean +/- SD]). These data suggest that the 15-lipoxygenase is enzymatically active on endogenous substrates in young human lesions and thus, may be of patho-physiological importance for early atherogenesis. In advanced human plaques the 15-lipoxygenase may be functionally silent and specific lipoxygenase products formed in earlier stages may be decomposed or superimposed by large amounts of nonenzymatic lipid peroxidation products.
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PMID:In vivo action of 15-lipoxygenase in early stages of human atherogenesis. 906 46

Increasing evidence suggests that phospholipid peroxidation plays important roles in the pathogenesis of various diseases, such as atherosclerosis. With regard to the biochemical processes that initiate phospholipid peroxidation in vivo, enzymatic conversion of phosphatidylcholine to phosphatidylcholine hydroperoxide (PCOOH) by lipoxygenase (LOX) may play a crucial role. This will become clear if we can analyze PCOOH bearing hydroperoxy fatty acids with S-stereoconfiguration. In this study, we therefore attempted such an analysis. Initially, we used LOX, linoleic acid and Lyso phosphatidylcholine, and synthesized PCOOH bearing 13S-hydroperoxy-9Z,11E-octadecadienoic acid (13(S)-9Z,11E-HPODE). PCOOH bearing racemic 13-9Z,11E-HPODE was also prepared. We used liquid chromatography equipped with CHIRALPAK OP (+) (poly (o-pyridyl diphenylmethacrylate) coated on silica), a UV detector and a quadrupole-time-of-flight mass spectrometer, and achieved diastereomer separation of PCOOH stereoisomers with excellent resolution and peak shape. This is the first study reporting the diastereomer separation of PCOOH. The present method will be beneficial in developing a better understanding of the biochemical processes that initiate oxidative stress (PCOOH formation) in vivo, which may lead to further elucidation of the involvement of PCOOH in the development of diseases. In addition to clinical applications, the present method may also be effective in the evaluation of enzymatic oxidative food deterioration.
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PMID:Direct separation of the diastereomers of phosphatidylcholine hydroperoxide bearing 13-hydroperoxy-9Z,11E-octadecadienoic acid using chiral stationary phase high-performance liquid chromatography. 2568 57