4-Hydroxynonenal induces dysfunction and apoptosis of cultured endothelial cells.

Lipolytic products of triglyceride-rich lipoproteins, i.e., free fatty acids, may cause activation and dysfunction of the vascular endothelium.

Arachidonic acid-induced oxidative injury to cultured spinal cord neurons.

Spinal cord trauma can cause a marked release of free fatty acids, in particular, arachidonic acid (AA), from cell membranes. Free fatty acids, and AA by itself, may lead to secondary damage to spinal cord neurons. To study this hypothesis, cultured spinal cord neurons were exposed to increasing concentrations of AA (0.

13-HPODE and 13-HODE modulate cytokine-induced expression of endothelial cell adhesion molecules differently.

Expression of cellular adhesion molecules (CAMs) at endothelial surfaces represents a physiological response to vascular damage and mediates the initiation of inflammation and possibly of atherogenesis. The cytokines TNF alpha and IL-1 are potent inducers of CAMs in endothelial cells. Reactive oxygen species comprising lipid oxidation products have been implicated in the signaling pathways of both TNF alpha and IL-1 and accordingly could modulate atherogenic events.

Antioxidant-like properties of zinc in activated endothelial cells.

Objective: The objective of this study was to test the hypothesis that zinc deficiency in endothelial cells may potentiate the inflammatory response mediated by certain lipids and cytokines, possibly via mechanisms associated with increased cellular oxidative stress. Our experimental approach was to compare conditions of cellular zinc deficiency and zinc supplementation with oxidative stress-mediated molecular and biochemical changes in vascular endothelial cells.

Methods: To investigate our hypothesis, porcine pulmonary artery-derived endothelial cells were depleted of zinc by culture in media containing 1% fetal bovine serum for eight days.

The role of linoleic acid in endothelial cell gene expression. Relationship to atherosclerosis.

There is evidence that linoleic acid plays a critical role in gene expression and vascular function as it relates to the pathogenesis of atherosclerosis. The lipid environment, particularly linoleic acid and its derivatives, of the vascular endothelium may profoundly influence the inflammatory response mediated by cytokines. Modulations in the level of activity of a select set of endothelial transcription factors appear to provide a mechanism for linking lipid/cytokine-mediated vessel wall dysfunction, including endothelial cell activation, altered proteoglycan metabolism, and endothelial barrier dysfunction, with the onset of atherosclerotic lesion formation.

Linoleic acid amplifies polychlorinated biphenyl-mediated dysfunction of endothelial cells.

Selected dietary lipids may increase the atherogenicity of environmental chemicals, such as polychlorinated biphenyls (PCBs), by cross-amplifying mechanisms leading to dysfunction of the vascular endothelium. To investigate this hypothesis, cultured endothelial cells were treated with 90 microM linoleic acid (18:2n-6), followed by either one of two PCBs, 3,3',4,4'-tetrachlorobiphenyl (PCB 77) or 2,2'4,4',5,5'-hexachlorobiphenyl (PCB 153). These PCBs were selected for their varying binding activities with the aryl hydrocarbon (Ah) receptor and differences in their induction of cytochrome P450.

Polyamine regulatory processes and oxidative stress in monocrotaline-treated pulmonary artery endothelial cells.

Alterations in polyamine metabolism may be a critical mechanism of monocrotaline (MCT)-induced structural remodeling of the pulmonary vasculature. In the present study, the hypothesis that MCT, through the induction of oxidative stress, modulates cellular polyamine regulatory mechanisms which in turn might be involved in the upregulation of fibronectin production in pulmonary artery endothelial cells (PAEC) was examined. A 24-h treatment with MCT significantly increased PAEC polyamine concentrations as compared to vehicle-treated cells.

Effect of linoleic acid on endothelial cell inflammatory mediators.

Selected lipids may influence the inflammatory cascade within the vascular endothelium. To test this hypothesis, endothelial cells were treated with linoleic acid (18:2, n - 6) for 12 hours and/or tumor necrosis factor-alpha (TNF) for 4 hours. For a combined exposure to 18:2 and TNF (18:2 + TNF), cells were first preenriched with 18:2 for 8 hours before exposure to TNF for an additional 4 hours.

Linoleic acid potentiates TNF-mediated oxidative stress, disruption of calcium homeostasis, and apoptosis of cultured vascular endothelial cells.

Diet-derived lipids may influence cytokine-mediated endothelial cell dysfunction, including TNF-induced apoptosis. To test this hypothesis, oxidative stress, intracellular calcium levels, endothelial barrier function, cell viability, and apoptosis were measured in vascular endothelial cells treated with 90 microM linoleic acid (18:2, n-6) and/or 20 ng/mL TNF (100 U/mL). For short-term exposure, endothelial cells were exposed to 18:2 for 6 h or to TNF for 1.

Zinc attenuates tumor necrosis factor-mediated activation of transcription factors in endothelial cells.

Objective: The objective of the study was to test the hypothesis that zinc can protect against endothelial dysfunction by interfering with oxidative stress-mediated cellular signaling and subsequent inhibition of an endothelial cell inflammatory response. Our approach was to compare alterations on molecular and biochemical levels with changes in endothelial barrier function that occur in zinc deficient conditions.

Methods: To investigate our hypothesis, endothelial cells were exposed to zinc deficient media for 2 to 10 days to deplete cellular zinc stores.

Oxidative stress mediates monocrotaline-induced alterations in tenascin expression in pulmonary artery endothelial cells.

Oxidative stress may be involved in monocrotaline (MCT)-induced endothelial cell injury and upregulation of extracellular matrix proteins in the pulmonary vasculature. To test this hypothesis, cytotoxicity, expression and distribution of tenascin (TN) as well as cellular oxidation were determined in porcine pulmonary artery endothelial cells (PAECs) exposed to MCT and/or to an oxygen radical scavenger, dimethylthiourea (DMTU). Relative to controls, treatment with 2.

Amyloid beta-peptide induces cell monolayer albumin permeability, impairs glucose transport, and induces apoptosis in vascular endothelial cells.

Amyloid beta-peptide (A beta) is deposited as insoluble fibrils in the brain parenchyma and cerebral blood vessels in Alzheimer's disease (AD). In addition to neuronal degeneration, cerebral vascular alterations indicative of damage to vascular endothelial cells and disruption of the blood-brain barrier occur in AD. Here we report that A beta25-35 can impair regulatory functions of endothelial cells (ECs) from porcine pulmonary artery and induce their death.

Aortic antioxidant defense and lipid peroxidation in rabbits fed diets supplemented with different animal and plant fats.

Objective: To test the hypothesis that dietary fats, depending on the fat source, may modulate aortic lipid peroxidation and antioxidant protection.

Methods: Rabbits were fed a low fat (LF, 2 g/100 g corn oil) diet or LF enriched with 16 g/100 g (w/w) of corn oil (CO), corn oil plus cholesterol (23.5 mg/100 g diet, CO + C), bovine milk fat (MF), chicken fat (CF), beef tallow (BT) or lard (L).

Is endothelial cell autocrine production of tumor necrosis factor a mediator of lipid-induced endothelial dysfunction?

Injury or dysfunction of the vascular endothelium is one of the first events in the development of atherosclerosis. Individual lipids, e.g.

Antiatherogenic properties of zinc: implications in endothelial cell metabolism.

Zinc is an essential component of biomembranes and is necessary for maintenance of membrane structure and function. There is evidence that zinc can provide antiatherogenic properties by preventing metabolic physiologic derangements of the vascular endothelium. Because of its antioxidant and membrane-stabilizing properties, zinc appears to be crucial for the protection against cell-destabilizing agents such as polyunsaturated lipids and inflammatory cytokines.

Nutritional implications in vascular endothelial cell metabolism.

Endothelial cells interact with blood components and the abluminal tissues, thus playing an active role in many aspects of vascular function. Numerous physiologic and pathophysiologic stimuli are often mediated by nutrients that can contribute to the overall functions of endothelial cells in the regulation of vascular tone, coagulation, cellular growth, immune and inflammatory responses. Therefore, nutrient-mediated functional changes of the endothelium and the underlying tissues may be significantly involved in disease processes such as atherosclerosis.

Increased lipid peroxidation and antioxidant activity in methionine-induced hepatitis in rabbits.

The liver is especially susceptible to the toxic effects of methionine due to its role in sulfur amino acid metabolism. Therefore, the excessive amounts of this amino acid may induce liver damage. To test the mechanisms of methionine-related hepatotoxicity, liver thiobarbituric acid reactive substances (TBARS), and activities of superoxide dismutase, catalase and selenium-dependent glutathione peroxidase were measured in rabbits fed a methionine-enriched diet for 6 or 9 mo.

Susceptibility to hepatic oxidative stress in rabbits fed different animal and plant fats.

Objective: This study was designed to determine the effect of diets enriched with plant and animal fats on oxidative stress and glutathione metabolism in rabbit liver tissues. This study was conducted to investigate whether the type of dietary fat will impact fatty acid composition and oxidant/antioxidant status in tissues.

Methods: Rabbits were fed diets containing 2 g corn oil/100 g diet (low fat diet, LF) and LF supplemented with 16 g/100 g diet of either corn oil (CO), CO with added cholesterol (CO + C), milk fat (MF), chicken fat (CF), beef tallow (BT), or lard (L) for 30 days.

Linoleic acid activates nuclear transcription factor-kappa B (NF-kappa B) and induces NF-kappa B-dependent transcription in cultured endothelial cells.

High dietary intakes of unsaturated fats may be atherogenic by disrupting normal functions of the vascular endothelium, due in part to the ability of linoleic acid (18:2n-6) to contribute to an increase in cellular oxidative stress and related injurious events. Exposing endothelial cells to 90 micromol linoleic acid/L for 6 h resulted in a significant increase in lipid hydroperoxides that coincided wih an increase in intracellular calcium concentrations. Treatment with this fatty acid caused an initial decrease in glutathione concentrations, which was followed by an increase at later time points.

Linoleic acid and TNF-alpha cross-amplify oxidative injury and dysfunction of endothelial cells.

Factors implicated in the development of atherosclerosis include metabolic alterations of the endothelium induced by certain lipids and inflammatory cytokines. To study the hypothesis that the combined presence of unsaturated fatty acids and inflammatory cytokines may cross-amplify their individual injurious effects, cultured endothelial cells were treated with 90 mu M of linoleic acid (18:2 n-6) and/or 20 ng/ml (100 U/ml) of tumor necrosis factor-alpha (TNF) for up to 24 h. Disturbances in endothelial cell metabolism were determined by measuring cellular oxidative stress, oxidative stress-inducible nuclear factor-kappa B (NF-kappa B) and NF-kappa B-related transcription, intracellular calcium levels, and endothelial barrier function reflected by transendothelial albumin movement.

Role of glutathione redox cycle in TNF-alpha-mediated endothelial cell dysfunction.

Modulation of the glutathione redox cycle may influence tumor necrosis factor-alpha (TNF)-mediated disturbances of endothelial integrity. To test this hypothesis, normal endothelial cells or cells with either increased or decreased glutathione levels were exposed to 100 ng (500 U) TNF/ml. Increased glutathione levels were achieved by exposure to 0.

Exposure to polychlorinated biphenyls causes endothelial cell dysfunction.

Environmental chemicals, such as polychlorinated biphenyls (PCBs), may be atherogenic by disrupting normal functions of the vascular endothelium. To investigate this hypothesis, porcine pulmonary artery-derived endothelial cells were exposed to 3,3',4,4'-tetrachlorobiphenyl (PCB 77), 2,3,4,4',5-pentachlorobiphenyl (PCB 114), or 2,2',4,4',5,5'-hexachlorobiphenyl (PCB 153) for up to 24 hours. These PCBs were selected for their varying binding avidities with the aryl hydrocarbon (Ah) receptor and differences in their induction of cytochrome P450.

Animal and plant fats selectively modulate oxidizability of rabbit LDL and LDL-mediated disruption of endothelial barrier function.

Enrichment of lipoproteins with fatty acids derived from animal and/or plant fats may modify the oxidizability of lipoproteins and their effects on endothelial barrier function. To test this hypothesis, rabbits were fed for 30 days diets containing 2 g corn oil/100 g diet (low fat diet) or low fat supplemented with 16 g/100 g diet of corn oil, corn oil with added cholesterol, milk fat, chicken fat, beef tallow or lard. Compared with those fed the low fat, serum and LDL cholesterol concentrations were significantly lower in rabbits fed corn oil and greater in animals fed corn oil with added cholesterol or chicken fat.

Increased lipid peroxidation as a mechanism of methionine-induced atherosclerosis in rabbits.

Methionine is converted by the transmethylation/transsulfuration pathway to homocysteine which may exert atherogenic effects by several mechanisms, including lipid peroxidation. Therefore, the excessive dietary methionine may induce the development of atherosclerosis. To test this hypothesis, plasma and aortic thiobarbituric acid reactive substances (TBARS), as well as activities of aortic and erythrocyte superoxide dismutase (SOD), catalase and selenium-dependent glutathione peroxidase (GPX) were measured in rabbits fed a diet enriched with 0.

Influence of nutrients and cytokines on endothelial cell metabolism.

The vascular endothelium plays an active role in physiological processes such as hemostasis, regulation of vessel tone and vascular permeability. Cell injury, or any event which disrupts endothelial integrity and thus endothelial permeability properties, may be involved in the early events leading to atherosclerotic lesion formation. Because of its constant exposure to blood components, including prooxidants, diet-derived fats and their derivatives, the endothelium is susceptible to oxidative stress and to injury mediated by blood lipid components.