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

In the present study performed on rats, we investigated the influence of an in vivo acute iron load on several platelet parameters and their modification after vitamin E supplementation. Iron load was achieved by injecting iron dextran corresponding to 0.1 mg Fe3+ per kg in the gluteus muscles. Control rats were injected with an equal amount of a dextran solution. Analyses were performed 18 h after injection. By comparison with controls, in iron-injected animals, we found significant increases of: (1) serum total iron (by 110%); (2) aggregation of isolated platelets induced by low concentration of thrombin and ADP (by 350% and 120%, respectively); (3) thrombin-induced endogenous serotonin secretion (by 94%). We also studied the mobilization of radiolabeled arachidonate preincorporated into platelet phospholipids. The results indicated that the thrombin-stimulated release of arachidonate and formation of cyclooxygenase and lipoxygenase products (particularly thromboxane B2), were significantly increased. We also found in plasma an increase (by 67%) of malondialdehyde (MDA) as well as a decrease of vitamin E (by 60%). When vitamin E was injected the day before iron injection, platelet hyperactivity and thromboxane biosynthesis were reduced as well as the plasma MDA concentration. Consequently, given the key role of calcium flux in the activation processes in platelets, we also investigated the thrombin-induced Ca2+ uptake by means of radiocalcium. We found that in platelets from iron-treated rats the Ca2+ uptake amounted to 3670 +/- 201 pmol/10(9) platelets (plt) and was significantly different from controls (1680 +/- 192 pmol/10(9) plt, P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1992 Oct
PMID:Effect of vitamin E on acute iron load-potentiated aggregation, secretion, calcium uptake and thromboxane biosynthesis in rat platelets. 146 49

Consumption of carotenoids is associated with an enhanced immune response and protection against neoplasia and atherosclerosis. Because these effects have been achieved using carotenoids with no pro-vitamin A activity, they are assumed to be due to the antioxidant properties of carotenoids. Carotenoids protect against photosensitized oxidation by quenching singlet oxygen. In addition, beta-carotene reacts chemically with peroxyl radicals to produce epoxide and apocarotenal products. To investigate the potential significance of these reactions to biological systems, we have used soybean lipoxygenase to generate peroxyl radical enzymatically. beta-Carotene inhibits the oxidation of linoleic acid by soybean lipoxygenase as well as the formation of the hydroperoxide product. In addition, the absorption of beta-carotene is diminished (bleached) by soybean lipoxygenase. The potential significance of these antioxidant reactions of carotenoids to biological function is discussed.
 ...
PMID:Carotenoids as cellular antioxidants. 157 92

This bird's eye view presents connections between the metabolically short-lived local hormones (collectively known as eicosanoids) and atherosclerotic cardiovascular disease. The discussion will be centered around an overview of coronary atherosclerosis with an emphasis on the sequences involved in the formation of atherosclerotic lesions; structure and historical background of oxygenated fatty acids cyclooxygenase and lipoxygenase products--eicosanoids; the generation of free radicals during the formation of endoperoxides by cyclooxygenase; the involvement of eicosanoids in the atherosclerotic inflammatory process, and finally, the effects of non-steroidal and steroidal anti-inflammatory drugs on the synthesis of eicosanoids and experimental atherosclerosis. Little is known about the exact role of eicosanoids in the genesis of atherosclerosis.
 ...
PMID:Atherosclerosis: the eicosanoid connection. 158 37

Reduced prostacyclin (PGI2) production by the vascular wall may play an important role in the pathogenesis of vascular lesions such as atherosclerosis. The present study was undertaken to evaluate the effect of vitamin E on the production of PGI2 and other prostaglandins (prostaglandin E2 [PGE2], thromboxane A2 [TXA2], and 15-hydroxyeicosatetraenoic acid [15-HETE]) by bovine aortic endothelial cells cultured in a high concentration of glucose (300 mg/dL). Compared with endothelial cells cultured in 100 mg/dL glucose, the production of PGI2 and other prostaglandins, except 15-HETE, was significantly reduced in cultures containing 300 mg/dL glucose when stimulated by histamine, the Ca2+ ionophore, A23187, or human plasma-derived serum (PDS). The addition of vitamin E to each stimulant significantly restored the production of PGI2, PGE2, and TXA2, products of the cyclo-oxygenase pathway, in aortic endothelial cells cultured in 300 mg/dL glucose. This effect of vitamin E on the stimulation of prostaglandin production was generally specific for D-alpha-tocopherol, but not for the other vitamin E analogs tested. However, vitamin E and the stimulants had no effect on the production of 15-HETE, a product of the lipoxygenase pathway. Moreover, vitamin E alone, without stimulants, did not affect prostaglandin production in cultured bovine aortic endothelial cells. These results suggest that vitamin E may restore reduced PGI2, PGE2, or TXA2 production by bovine aortic endothelial cells cultured in a high concentration of glucose. It seems likely that vitamin E may restore depressed PGI2 production by the vascular wall in hyperglycemic conditions such as those seen in patients with diabetes mellitus.
 ...
PMID:Vitamin E restores reduced prostacyclin synthesis in aortic endothelial cells cultured with a high concentration of glucose. 164 Aug 48

The immunoreactivity of human apolipoprotein B (apo B) towards 5 monoclonal antibodies was studied by enzyme immunoassay in native and in vitro oxidized low density lipoproteins (LDL). LDL oxidative modifications were obtained by incubation with either copper ions or an association of lipoxygenase and phospholipase A2. The monoclonal antibodies used in the inhibition analysis were directed to epitopes located in the amino-terminal region (1D1), in the middle part (2D8, L7, 4G3) and in the carboxy-terminal region (L3) of the apo B molecule. The results demonstrated that the immuno-reactivity of 1D1 epitope was little affected by LDL oxidation with copper ions or lipoxygenase plus phospholipase A2, whereas the immunoreactivity of the other epitopes were markedly decreased by these LDL modifications. Immunoreactivity changes were more important in L3 and L7 epitopes than in 2D8 and 4G3 epitopes. Since it is known that L3 and L7 epitopes are located in apo B domains rich in lipid-associated peptides whereas 1D1 is in a domain poor in such peptides, these results suggest a relationship between the lipid environment of an apo B epitope and its susceptibility to alteration by LDL oxidation.
Atherosclerosis 1991 Jul
PMID:Resistance to LDL oxidative modifications of an N-terminal apolipoprotein B epitope. 172 77

The oxidative modification of low density lipoprotein (LDL) may play an important role in the pathogenesis of atherosclerosis. LDL can be oxidatively modified in vitro by endothelial cells, mouse peritoneal macrophages, or copper ions. Studies using lipoxygenase inhibitors have suggested that lipoxygenase(s) is required for the cellular modification of LDL [Rankin, S. M., Parthasarathy, S. & Steinberg, D. (1991) J. Lipid Res. 32, 449-456]. We have reexamined the effect of lipoxygenase inhibitors on cellular modification and found that (i) inhibitors specific for 5-lipoxygenase do not block LDL modification; (ii) inhibitors that block lipoxygenase by donating one electron to the enzyme (reductive inactivation) prevent LDL modification by cells and also modification mediated by copper ions, implying that they act as general antioxidants; (iii) the lipoxygenase inhibitor 5,8,11,14-eicosatetraynoic acid blocks 15-lipoxygenase activity in intact macrophages at concentrations 100 times less than those required to block LDL modification by macrophages; and (iv) 5,8,11,14-eicosatetraynoic acid is cytotoxic at concentrations about twice those required to prevent modification. Furthermore, macrophages and the RECB4 line of endothelial cells modify LDL with similar efficiencies despite dramatic differences in 15-lipoxygenase activity. Thus we conclude that neither 5-lipoxygenase nor 15-lipoxygenase is required for modification of LDL by cultured cells.
 ...
PMID:Cellular oxidative modification of low density lipoprotein does not require lipoxygenases. 172 78

Arachidonate 15-lipoxygenase (arachidonate:oxygen 15-oxidoreductase, EC 1.13.11.33) is a lipid-peroxidating enzyme that is implicated in oxidizing low density lipoprotein to its atherogenic form. Monocyte/macrophage 15-lipoxygenase is present in human atherosclerotic lesions. To pursue a basis for induction of the enzyme, which is not present in blood monocytes, the ability of relevant cytokines to regulate its expression was investigated. Interleukin 4 (IL-4), among 16 factors tested, specifically induced 15-lipoxygenase mRNA and protein in cultured human monocytes. Interferon gamma and hydrocortisone inhibited this induction. High-performance liquid chromatography analysis of lipid extracts from IL-4-treated monocytes detected 15-lipoxygenase products esterified to the cellular membrane lipids, indicating enzymatic action on endogenous substrates. Stimulation of IL-4-treated monocytes with calcium ionophore or opsonized zymosan A enhanced the formation of 15-lipoxygenase products. These data identify IL-4 and interferon gamma as physiological regulators of lipoxygenase expression and suggest an important link between 15-lipoxygenase function and the immune/inflammatory response in atherosclerosis as well as other diseases.
 ...
PMID:Specific inflammatory cytokines regulate the expression of human monocyte 15-lipoxygenase. 172 92

Silymarin is the flavonoids extracted from the seeds of Silybum marianum (L) Gearth as a mixture of three structural isomers: silybin, silydianin and silychristin, the former being the most active component. Silymarin protects liver cell membrane against hepatotoxic agents and improves liver function in experimental animals and humans. It is generally accepted that silymarin exerts a membrane-stabilizing action preventing or inhibiting membrane peroxidation. The experiments with soybean lipoxygenase showed that the three components of silymarin brought about a concentration-dependent non-competitive inhibition of the lipoxygenase. The experiments also showed an analogous interaction with animal lipoxygenase, thus showing that an inhibition of the peroxidation of the fatty acid in vivo was self-evident. Silybin almost completely suppressed the formation of PG at the highest concentration (0.3 mM) and proved to be an inhibitor of PG synthesis in vitro. In our experiments, silybin at lower dose (65 mg/kg) decreased liver lipoperoxide content and microsomal lipoperoxidation to 84.6% and 68.55% of those of the scalded control rats respectively, and prevented the decrease of liver microsomal cytochrome p-450 content and p-nitroanisole-O-demethylase activity 24 h post-scalding. Effects of silymarin on cardiovascular system have been studied in this university since 1980. P. O silymarin 800 mg/kg/d or silybin 600 mg/kg/d reduced plasma total cholesterol, LDL-C and VLDL-C. They however, enhanced HDL-C in hyperlipemic rats. Further studies showed that silymarin enhanced HDL-C but didn't affect HDL-C, a property of this component which is beneficial to treatment of atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Advances in pharmacological studies of silymarin. 184 18

Arachidonic acid metabolism via cyclooxygenase, lipoxygenase, and cytochrome P-450 epoxygenase was investigated in thoracic aortic tissue obtained from rabbits fed either standard rabbit chow or chow containing 2% cholesterol. Aortic strips were incubated with [14C]arachidonic acid and A23187. Metabolites from extracted media were resolved by high-pressure liquid chromatography (HPLC). Normal and cholesterol-fed rabbit aortas synthesized prostaglandins (PGs) and hydroxyeicosatetraenoic acids (HETEs). The major cyclooxygenase products were 6-keto-PGF1 alpha and PGE2. Basal aortic 6-keto-PGF1 alpha production was slightly reduced in cholesterol-fed compared with normal rabbits. 12(S)- and 15(S)-HETE were the major aortic lipoxygenase products from both normal and cholesterol-fed rabbits. The structures were confirmed by gas chromatography-mass spectrometry (GC-MS). Only cholesterol-fed rabbit aortas metabolized arachidonic acid via cytochrome P-450 epoxygenase to the epoxyeicosatrienoic acids (EETs). 14,15-, 11,12-, 8,9-, and 5,6-EET were identified based on comigration on HPLC with known 14C-labeled standards and typical mass spectra. Incubation of normal aorta with 14,15-EET decreased the basal synthesis of 6-keto-PGF1 alpha. The other EETs were without effect. The four EET regioisomers relaxed the norepinephrine-precontracted normal and cholesterol-fed rabbit aorta. The relaxation response to 14,15-EET was greater in aortas from cholesterol-fed rabbits. These studies demonstrate that hypercholesterolemia, before the development of atherosclerosis, alters arachidonic acid metabolism via both the cyclooxygenase and epoxygenase pathways.
 ...
PMID:Enhanced synthesis of epoxyeicosatrienoic acids by cholesterol-fed rabbit aorta. 188 29

Arachidonate 15-lipoxygenase (an n-6 lipoxygenase) has been purified to homogeneity, cloned and expressed and appears to be a highly regulated enzyme showing pronounced tissue specificity. The enzyme is expressed prominently in the reticulocyte where it appears to be under posttranscriptional control and may play a key physiological role in reticulocyte maturation by initiating mitochondrial breakdown. 15-Lipoxygenase is also expressed in significant quantities in airway epithelial cells and eosinophils although no clear role for this enzyme in these cell types has been defined. The enzyme catalyzes the conversion of free arachidonic acid to 15-HPETE, free linoleic acid to 13-HPOD and can also oxygenate polyenoic acids esterified in phospholipids. A number of potential physiological and pathological roles for products of this enzyme have been postulated. These include a physiological role in prolactin secretion from pituitary cells and in the initiation of the acrosome reaction in spermatozoa. An important pathological role in the oxidation of LDL by macrophages has also been proposed, indicating that the enzyme could be a pharmacological target for the treatment of atherosclerosis.
 ...
PMID:Arachidonate 15-lipoxygenase; characteristics and potential biological significance. 191 Aug 64


1 2 3 4 5 6 7 8 9 10 Next >>