Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A model of early atherosclerosis in hamsters with moderate hypercholesterolemia (217 to 271 mg/dL) was established that was highly responsive to exogenous antioxidants. A key feature of this model was elevation of vascular oxidative stress by use of a diet deficient in nutritional antioxidants and supplemented with corn oil (10%) and cholesterol (0.2%, 0.4%, or 0.8%). After 10 weeks on the 0.4% cholesterol diet, mean plasma alpha-tocopherol levels declined from 5.68 +/- 0.30 to 1.27 +/- 0.15 micrograms/mL, while monocyte-macrophage foam cell lesions in the aortic arch, as assayed by video microscopy/image analysis of oil red O-stained histological specimens, increased from undetectable at week 0 to 60,900 +/- 5400 microns 2 per specimen at week 10 (mean +/- SEM, n = 36). alpha-Tocopherol or probucol administered for 10 weeks markedly suppressed LDL oxidation ex vivo and profoundly inhibited aortic foam cell formation. However, the effects of antioxidants on aortic lesions were attenuated at higher plasma cholesterol levels, although LDL oxidation ex vivo was effectively inhibited. With a plasma cholesterol level at approximately 250 mg/dL, the maximum effect of alpha-tocopherol on lesion size reached approximately 36% of control value, and the dose for half-maximal effect was approximately 10 mg.kg-1.d-1, which resulted in a plasma alpha-tocopherol value of approximately 20 micrograms/mL. Under these conditions a linear, inverse correlation of aortic lesion size and plasma alpha-tocopherol concentration was observed (n = 68, r = -0.581, P < .001). The data demonstrate that LDL oxidation is a significant component of early atherogenesis in this model but suggest that hyperlipidemia can outweigh the therapeutic effectiveness of antioxidants. The high sensitivity of aortic lesion initiation to alpha-tocopherol in hamsters maintained on moderately hypercholesterolemic diets depleted of endogenous antioxidants demonstrates that vascular oxidative stress can be isolated from other causative factors in an in vivo model of atherosclerosis.
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PMID:Relation of vascular oxidative stress, alpha-tocopherol, and hypercholesterolemia to early atherosclerosis in hamsters. 774 45

It was reported that free fatty acids degraded from triglycerides by lipase may play a major role in acute necrotizing or hyperlipidemia-induced pancreatitis. We hypothesized that this injury may be related to the peroxidation of cell membrane phospholipids and tested this hypothesis using isolated pancreatic acini. Pancreatic acini were prepared from male Sprague-Dawley rats by collagenase digestion. Linoleic acid was added (0.1-1.0 mM) to the acinar cell suspension to induce cell injury. Acinar cell damage was measured by lactate dehydrogenase release and by trypan blue exclusion. Phosphatidylcholine hydroperoxide and alpha-tocopherol in the acinar cells were measured. Protective effects of alpha-tocopherol (0.5, 5.0 mM) against this type of cell injury were also evaluated. When isolated acinar cells were treated with linoleic acid, a significant decrease in viability was observed in a time- and dose-dependent manner. In addition, the levels of phosphatidylcholine hydroperoxide after treatment of 0.5 mM of linoleic acid were increased and levels of alpha-tocopherol were decreased significantly. alpha-Tocopherol significantly ameliorated both cellular injury (p < 0.01) and increases in phosphatidylcholine hydroperoxide (p < 0.01). These data suggest that lipid peroxidation of the cellular membrane is an important component of the pancreatic cell injury mediated by free fatty acids.
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PMID:Involvement of lipid peroxidation in free fatty acid-induced isolated rat pancreatic acinar cell injury. 982 Nov 80

We investigated the redox dynamics of alpha-tocopherol in plasma and erythrocyte membranes in elderly patients with asymptomatic primary hyperlipidemia divided into three groups (hypercholesterolemia, hypertriglyceridemia and low high-density lipoprotein cholesterol levels) and in healthy elderly subjects to assess the antioxidative status of alpha-tocopherol. alpha-Tocopherol and alpha-tocopherolquinone were determined by high-performance liquid chromatography using a redox detection mode. In the erythrocyte membrane, there was no difference in the alpha-tocopherol concentration between hyperlipidemic and healthy subjects. The alpha-tocopherolquinone/alpha-tocopherol ratio in plasma and erythrocyte membrane, and the alpha-tocopherol in erythrocyte membrane/alpha-tocopherol in plasma ratio were significantly lower in elderly patients with hypercholesterolemia or hypertriglyceridemia. These findings suggest that the uptake ratio in erythrocyte membranes and the antioxidative activity of alpha-tocopherol in both plasma and erythrocyte membranes are decreased in elderly hyperlipidemic patients. These decreases may promote membrane lipid peroxidation or accelerate atherosclerosis.
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PMID:Redox dynamics of alpha-tocopherol in erythrocyte membranes of elderly patients with asymptomatic primary hyperlipidemia. 1038 22