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High linoleic acid, low vegetable, and high oleic acid, high vegetable diets affect platelet activation similarly in healthy women and men.

Upregulation of protein kinase C (PKC), an important enzyme in platelet activation, could be one step toward platelet hyperactivity. PKC activation can be modulated by dietary components in vitro, but few data are available concerning the in vivo effects. In this strictly controlled human dietary intervention, the influence of dietary unsaturated fatty acids and vegetable compounds on platelet activation was investigated. A high linoleic acid diet (10% of energy) with small amounts of vegetables (no berries or apples) was consumed by 9 women and 4 men (24.1 +/- 3.9 y), and was compared with a high oleic acid diet (12% of energy) with considerable amounts of vegetables, berries and apples consumed by 8 women and 4 men (24.2 +/- 5.5 y). Subjects were healthy Finnish volunteers. Compliance with the experimental protocol was good, as indicated by changes in plasma fatty acids and concentrations of vitamin C, beta-carotene and alpha-tocopherol. No differences between groups were seen in indices of platelet activation, including platelet aggregation, total PKC activity and distribution of PKC isoenzymes alpha, beta(II) and delta. The results indicate that in apparently healthy and fairly young subjects with adequate vitamin intakes, diets differing markedly in their amounts of linoleic and oleic acids, and vegetables, berries and apples do not differ in platelet activation.

Antioxidants↗

Contribution of conjugated linoleic acid to the suppression of inflammatory responses through the regulation of the NF-kappaB pathway.

Data from a number of researchers have shown that conjugated linoleic acid (CLA) has some beneficial health activities in animal models. Because inflammatory responses are associated with pathophysiology of many diseases, the aim of this study is to explore the effect and mechanism of CLA in the regulation of lipopolysaccharide (LPS)-induced inflammatory responses in RAW 264.7 macrophages. The addition of increasing levels of CLA proportionally augmented the incorporation of CLA in cultures. CLA diminished LPS-induced mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2) as well as subsequent production of nitric oxide and prostaglandin E(2), respectively. We further examined the effect of CLA on LPS-induced NF-kappaB activation by Western blot and the electrophoretic mobility shift assay. The addition of CLA at 200 microM significantly diminished LPS-induced protein expression of the cytoplasmic phosphorylated inhibitor kappaBalpha and nuclear p65 as well as NF-kappaB nuclear protein-DNA binding affinity. In conclusion, our data suggest that CLA may inhibit LPS-induced inflammatory events in RAW 264.7 macrophages and this inhibitory activity of CLA, at least in part, occurs through CLA modulating the NF-kappaB activation and therefore negatively regulating expression of inflammatory mediators.

Animals↗

Therapeutic effect of topical application of linoleic acid and lincomycin in combination with betamethasone valerate in melasma patients.

Melasma is an acquired symmetric hypermelanosis characterized by irregular light-to gray-brown macules and patches on sun-exposed areas. Many therapeutic agents are available but are unsatisfactory. Recently, it has been demonstrated that lincomycin (LM) and linoleic acid (LA) can inhibit melanogenesis in vitro. Our purpose was to investigate the clinical efficacy of topical application of LM and LA in combination with betamethasone valerate (BV) in melasma patients. Forty-seven Korean female adults with clinically diagnosed melasma were enrolled in a 6-week, double-blind, randomized clinical trial. Patients were treated with one application of the vehicle (group A), 2% LM mixed with 0.05% BV (group B), or 2% LM mixed with 0.05% BV and 2% LA (group C) on the face every night. Determination of efficacy was based on the Melasma Area and Severity Index (MASI) score and objective assessment (no effect, mild, moderate, or excellent) at intervals of 2 weeks until the end of the study at 6 weeks. After 6 weeks, in comparison with the pre-treatment MASI score, the average MASI score of group C decreased to 68.9%, compared with 98% in group A (p<0.05) and 85.4% in group B. There was no statistically significant difference between group A and group B. Seven patients (43.7%) in group C revealed more than moderate improvement in objective assessment, compared with none in group A and two patients (12.5%) in group B. There were no significant side effects. Topical application of linoleic acid is considered to be effective in the treatment of melasma patients.

Administration, Topical↗

Protection of conjugated linoleic acids against 2-amino-3- methylimidazo[4,5-f]quinoline-induced colon carcinogenesis in the F344 rat: a study of inhibitory mechanisms.

Grilled ground beef contains a number of heterocyclic amine carcinogens, such as 2-amino-3-methylimidazo[4,5-f] quinoline (IQ), as well as anticarcinogenic conjugated linoleic acids (CLA). In the present study, CLA was administered to male F344 rats by gavage on alternating days in weeks 1-4, while IQ was given by gavage every other day in weeks 3 and 4 (100 mg/kg body wt). Rats were killed 6 h after the final carcinogen dose 16 in order to score colonic aberrant crypt foci (ACF). In the ACF study, CLA had no effect on the size of the foci, but inhibited significantly (P < 0.05) the number of ACF/colon, from 4.3 +/- 2.4 in controls to 1.1 +/- 1.3 in CLA-treated rats (mean +/- SD, n = 10). Rats given CLA also had significantly lower IQ-DNA adducts in the colon as determined by 32P-postlabeling analysis; relative adduct labeling levels (RAL x 10(7) for the major adduct were 9.13 +/- 2.6 in controls versus 5.42 +/- 1.8 in CLA-treated animals (P < 0.05). Mechanism studies indicated that CLA and other fatty acids interact with certain heterocyclic amines in a manner consistent with substrate-ligand binding. However, no such interaction occurred with IQ, and CLA failed to inhibit significantly the mutagenicity of N-hydroxy-IQ in the Salmonella assay. Liver microsomes from CLA-treated rats exhibited lower activities for dealkylation of 7-ethoxyresorufin and methoxyresorufin and activated IQ to DNA binding species less effectively than microsomes from control animals. Direct addition of CLA to the in vitro incubation inhibited IQ-DNA binding and was associated with increased recovery of unmetabolized parent compound. In the Salmonella assay, CLA inhibited the mutagenic activity of IQ in the presence of S9 or ram seminal vesicle microsomes. Collectively, these results support a mechanism involving inhibition of carcinogen activation by CLA, as opposed to direct interaction with the procarcinogen, scavenging of electrophiles or selective induction of phase I detoxification pathways.

Animals↗

Effects of conjugated linoleic acid on growth performance, feed conversion efficiency, and subsequent carcass quality in broiler chickens.

The effect of dietary conjugated linoleic acid isomers (CLA) on growth performance, carcass composition, fatty acid composition of adipose and muscle tissues, and serum lipoproteins was investigated in broiler chickens. A total of 160 (eighty male and eighty female) chickens were allocated to four dietary treatments (0.0, 0.5, 1.0, and 1.5 % CLA) and fed a standard starter diet from 8 to 21 d, and a grower-finisher diet from 22-42 d. When determined for the total period 8-42 d, feed intake and body weight gains of broiler chickens were significantly reduced (from 3.31 to 3.12 kg and from 1615 to 1435 g respectively; P < 0.05), particularly at the 1.5 % dietary CLA level. Feed conversion efficiency and carcass yield values showed no significant effects of dietary CLA. Abdominal fat deposition was significantly reduced (from 2.68 to 1.78 %; P < 0.05), the relative proportion of breast muscles was unaffected, and that of leg muscles significantly increased (from 19.0 to 20.6 %; P < 0.05). The concentration of CLA isomers (% of total methyl esters of fatty acids) increased linearly in tissue samples from broilers fed 0.5, 1.0, and 1.5 % dietary CLA. The relative proportions of saturated fatty acids (16:0, 18:0) were significantly (P < 0.01) increased, and those of monounsaturated (16:1, 18:1) and polyunsaturated fatty acids (18:2, 20:4 in muscle tissues) significantly (P < 0.05) reduced. Total serum cholesterol concentrations reached a maximum in broilers fed 1.0 % CLA and then decreased slightly (from 141.73 to 136.47 mg/dl; P < 0.01). The same was true also for HDL-cholesterol (from 113.58 to 109.97 mg/dl; The HDL cholesterol:total cholesterol ratio and serum triacylglycerol concentration was unaffected. In conclusion, feeding CLA to broiler chickens resulted in substantial incorporation of CLA isomers into their tissue lipids, thus providing a potential CLA-rich source for human consumption.

Abdomen↗

In vivo conversion of linoleic acid to arachidonic acid in human adults.

Human adults are shown to be capable of conversion of linoleic acid (LA, 18:2 n-6) to arachidonic acid (AA, 20:4 n-6) in vivo. It is confirmed that they can also convert alpha-linolenic acid (LNA, 18:3 n-3) to eicosapentaenoic acid (EPA, 20:5 n-3) and to docosahexaenoic acid (DHA, 22:6 n-3) in vivo. The time course and the maximal response for these processes during the first week after a single dose of the 18-carbon precursor is described. A stable-isotope method in which the protons of the C17 and C18 carbons are substituted with deuterium atoms is used in order to provide for a safe method for the study of human metabolism. High sensitivity and selectivity of detection is assured with negative ion, gas chromatography/mass spectrometry analysis. It is clear that human adults on an ad lib diet carry out EFA metabolism in vivo.

Administration, Oral↗

Positional distribution of conjugated linoleic acid in triacylglycerol of Saccharomyces cerevisiae.

Saccharomyces cerevisiae was cultivated in the presence of cis-9,trans-11 or trans-10,cis-12 isomers of free conjugated linoleic acid (CLA), and the effects of the isomers on the regioisomerisms of triacylglycerol (TAG) of the yeast were elucidated. Both isomers constituted about 34% of all fatty acids and increased drastically the number of different TAG species. Nearly all of the species contained CLA in at least one sn-position. In the most abundant species analyzed (20% of total species), the cis-9,trans-11 isomer appeared in combination with monounsaturated fatty acids (C16:1, C:18:1) whereas trans-10,cis-12 isomer was most frequently present with a medium chain fatty acid (C10:0 or C12:0) in the sn-2 position and C16:0 in one of the end positions (14% of total species). With either isomer, the amount of TAG species in which CLA encompassed all sn-positions was ca. 4%. Thus, S. cerevisiae can be used to produce edible single cell oil characterized by very heterogeneous distribution of CLA among the different TAG species.

Fatty Acids↗

Effect of dietary conjugated linoleic acid (CLA) on lipid composition, metabolism and gene expression in Atlantic salmon (Salmo salar) tissues.

Dietary conjugated linoleic acid (CLA) affects fat deposition and lipid metabolism in mammals, including livestock. To determine CLA effects in Atlantic salmon (Salmo salar), a major farmed fish species, fish were fed for 12 weeks on diets containing fish oil or fish oil with 2% and 4% CLA supplementation. Fatty acid composition of the tissues showed deposition of CLA with accumulation being 2 to 3 fold higher in muscle than in liver. CLA had no effect on feed conversion efficiency or growth of the fish but there was a decreased lipid content and increased protein content after 4% CLA feeding. Thus, the protein:lipid ratio in whole fish was increased in fish fed 4% CLA and triacylglycerol in liver was decreased. Liver beta-oxidation was increased whilst both red muscle beta-oxidation capacity and CPT1 activity was decreased by dietary CLA. Liver highly unsaturated fatty acid (HUFA) biosynthetic capacity was increased and the relative proportion of liver HUFA was marginally increased in salmon fed CLA. CLA had no effect on fatty acid Delta6 desaturase mRNA expression, but fatty acid elongase mRNA was increased in liver and intestine. In addition, the relative compositions of unsaturated and monounsaturated fatty acids changed after CLA feeding. CLA had no effect on PPARalpha or PPARgamma expression in liver or intestine, although PPARbeta2A expression was reduced in liver at 4% CLA feeding. CLA did not affect hepatic malic enzyme activity. Thus, overall, the effect of dietary CLA was to increase beta-oxidation in liver, to reduce levels of total body lipid and liver triacylglycerol, and to affect liver fatty acid composition, with increased elongase expression and HUFA biosynthetic capacity.

Animals↗

Preferential incorporation of trans, trans-conjugated linoleic acid isomers into the liver of suckling rats.

The present study was designed to compare the conjugated linoleic acid (CLA) isomeric distribution pattern in the liver of suckling rats in relation to those in the milk and maternal diet. Silver-ion HPLC was used to separate individual CLA isomers. It was found that the isomeric distribution pattern in the milk was very similar to that in the maternal dietary fat. However, the CLA isomeric distribution patterns in the liver phospholipids (PL) and triacylglycerols were different from those in the diet and milk. In the liver PL, total cisltrans isomers accounted for 63.6-63.9% of total CLA, which was in contrast to the values of 88.1-89.1% in the milk and diet. In the liver PL, total transltrans isomers were 20.6-20.8% of the total CLA isomers whereas they were only 2.6-3.7% in the milk and diet. It is concluded that trans/trans-CLA were preferentially incorporated into the liver whereas for the incorporation of cis/trans-CLA there was partial discrimination.

Animals↗

Intake of conjugated linoleic acid, fat, and other fatty acids in relation to postmenopausal breast cancer: the Netherlands Cohort Study on Diet and Cancer.

BACKGROUND: Conjugated linoleic acid (CLA), which is present in milk products and meat from ruminants, appears to have anticarcinogenic activity against breast cancer in animal and in vitro experiments. To date, few epidemiologic data are available in humans. OBJECTIVE: This study evaluated the relation between intakes of CLA and other fatty acids and breast cancer incidence in the Netherlands Cohort Study. DESIGN: Intake data derived from a validated 150-item food-frequency questionnaire were linked to an existing database with analytic data on specific fatty acids in European foods (the TRANSFAIR study). With 6.3 y of follow-up and 941 incident cases of breast cancer, multivariate rate ratios and 95% CIs were calculated for energy-adjusted intakes of fatty acids and CLA-containing food groups (eg, butter, cheese, milk, other milk products, and meat). RESULTS: CLA intake showed a weak, positive relation with breast cancer incidence (rate ratio for highest compared with lowest quintile: 1.24, 95% CI: 0.91, 1.69; P for trend = 0.02). Statistically significant positive associations were found with total trans fatty acids and (borderline) with saturated fatty acids. Significant inverse associations were found with monounsaturated and cis unsaturated fatty acids, whereas total fat and energy intake of CLA-containing food groups were not related to breast cancer incidence. CONCLUSION: The suggested anticarcinogenic property of CLA in animal and tissue culture models could not be confirmed in this epidemiologic study in humans.

Aged↗

Production and metabolic responses of periparturient Holstein cows to dietary conjugated linoleic acid and trans-octadecenoic acids.

Thirty-eight multiparous Holstein cows were utilized in a completely randomized design to examine the effect of feeding calcium salts of conjugated linoleic acid (CLA) and trans-octadecenoic acids (trans-C18:1) on animal performance and lipid and glucose metabolism during the transition to lactation. Dietary treatments were initiated approximately 28 d prior to expected calving dates and continued through d 49 postpartum. Prepartum treatments consisted of 1) a basal diet (Control), 2) basal diet + 150 g/d of CLA mix (CLA), and 3) basal diet + 150 g/d of trans-C18:1 mix (TRANS). Amounts of calcium salts of CLA and trans-C18:1 mixes were adjusted to 225 g/d during the 49-d postpartum treatment period. All diets were offered as a total mixed ration. Prepartum fat supplementation had no detectable effects on dry matter intake, body weight, or body condition score. After parturition, cows in the TRANS group consumed less dry matter at wk 4, 5, and 6 of lactation than did cows in the control group. Cows fed the trans-C18:1 supplement were in a more severe negative energy balance than those fed the control diet at 1 wk of lactation. Periparturient fat supplementation had no detectable effects on milk yield during wk 1 to 7 of lactation. Milk fat was not affected during wk 1 to 4, but was reduced after wk 4 of lactation by dietary CLA. Feeding calcium salts of CLA decreased short- to medium-chain fatty acid (C4 to C14) concentrations and increased both linoleic and linolenic acid concentrations in milk fat. Concentrations of nonesterified fatty acids and beta-hydroxybutyric acid in blood were greater in cows fed the CLA-supplemented diet than in those fed the control diet at 1 wk of lactation. In spite of small numerical tendencies, hepatic lipid and triacylglycerol concentrations did not vary significantly among dietary treatments. Periparturient fat supplementation had no detectable effects on plasma glucose and insulin concentrations. Steady-state concentrations of hepatic mRNA encoding pyruvate carboxylase and phosphoenolpyruvate carboxykinase were greater for the TRANS treatment group than the control and CLA groups. Results indicate that dietary CLA and trans-C18:1 fatty acids may affect lipid and glucose metabolism in early postpartum Holstein cows through distinct mechanisms.

3-Hydroxybutyric Acid↗

Effect of plasma on the degradation of hydroperoxides of unesterified linoleic acid and copper-peroxidized LDL.

The determination of lipid hydroperoxides in plasma and lipoproteins recently reached a clinical relevance in disorders such as atherosclerosis, where oxidative reactions have been suggested to play a fundamental pathogenetic role. The peroxide content of lipoproteins is usually measured after ultracentrifugation and extraction. During this procedure, some peroxides might decompose causing a too low recovery. To screen this possibility, the disappearance, in the presence of human plasma, of hydroperoxides of linoleic acid and Cu-oxidized low density lipoprotein (LDL) have been investigated, using both a iodometric titration and an enzymatic assay. While only in the presence of GSH plasma decomposes linoleic acid hydroperoxides quite rapidly, peroxides in Cu-oxidized LDL were stable both in presence as well as in absence of GSH. This indicated that lipid hydroperoxides are stable in plasma and that peroxides of Cu-oxidized LDL are not substrate for the glutathione-dependent peroxidase activity in plasma. The relevant decrease of the iodometric titre of LDL peroxides observed in the presence of elevated amounts of plasma was shown to be artifactual, since some compounds extracted from plasma do react with iodine generated by peroxides. Whole plasma itself, indeed, has been shown to reduce back to I- appreciable amount of free iodine.

Copper↗

The effects of conjugated linoleic acids or an alpha-glucosidase inhibitor on tissue lipid concentrations and fatty acid composition of broiler chicks fed a low-protein diet.

The effects of dietary conjugated linoleic acid (CLA) and an alpha-glucosidase inhibitor--Bay g 5421--on tissue lipid concentrations and fatty acid composition were investigated in male broiler chicks fed a low-protein diet. The trial comprised six isoenergetic broiler diets. One diet (high-protein diet) was used as a control diet and contained 230 g crude protein per kilogram. The other five diets were low-protein diets (180 g crude protein/kg) without additional supplement, or supplemented with 20 or 40 g/kg of a CLA-enriched oil, or supplemented with 50 or 100 mg of Bay g 5421/kg. Broilers fed the low-protein diets had higher concentrations of triglycerides and cholesterol in the liver than broilers fed the high-protein diet. Broilers fed low-protein diets supplemented with CLA had a higher cholesterol concentration in plasma, lower hepatic triglyceride concentrations, higher relative concentrations of saturated fatty acids (SFA), and lower relative concentrations of monounsaturated fatty acids (MUFA) in lipids of liver, thigh muscle, and adipose than broilers fed low-protein diets without CLA supplement. Broilers fed the low-protein diets supplemented with Bay g 5421 had lower concentrations of triglycerides and cholesterol in the liver and lower concentrations of triglycerides in plasma than broilers fed the low-protein diet without supplementation. Moreover, broilers fed diets with Bay g 5421 had higher relative concentrations of polyunsaturated fatty acids and lower relative concentrations of MUFA in lipids of liver, muscle, and adipose tissue. The results show that supplementation of the low-protein diets with CLA and Bay g 5421 affected tissue lipid concentrations and fatty acid composition in broilers, which are of practical relevance with regards to meat quality.

Acarbose↗

Effects of conjugated linoleic acid (CLA) on immune responses, body composition and stearoyl-CoA desaturase.

Conjugated linoleic acid (CLA) has shown a wide range of biologically beneficial effects; reduction of incidence and severity of animal carcinogenesis, reduction of the adverse effects of immune stimulation, reduction of severity of atherosclerosis, growth promotion in young rats, and modulation of stearoyl-CoA desaturase (SCD). One of the most interesting aspects of CLA is its ability to reduce body fat while enhancing lean body mass which is associated with the trans-10,cis-12 isomer of CLA. The effects of CLA are unique characteristics that have not been observed with other polyunsaturated fatty acids. In this review, we will focus on the effects of CLA on immune responses, body compositional changes and stearoyl-CoA desaturase.

Animals↗

Lipoxygenase is irreversibly inactivated by the hydroperoxides formed from the enynoic analogues of linoleic acid.

Triple bond analogues of natural fatty acids irreversibly inactivate lipoxygenase during their enzymatic conversion [Nieuwenhuizen, W. F., et al. (1995) Biochemistry 34, 10538-10545]. To gain insight into the mechanism of the irreversible inactivation of soybean lipoxygenase-1, we studied the enzymatic conversion of two linoleic acid analogues, 9(Z)-octadec-9-en-12-ynoic acid (9-ODEYA) and 12(Z)-octadec-12-en-9-ynoic acid (12-ODEYA). During the inactivation process, Fe(III)-lipoxygenase converts 9-ODEYA into three products, i.e. 11-oxooctadec-9-en-12-ynoic acid, racemic 9-hydroxy-10(E)-octadec-10-en-12-ynoic acid, and racemic 9-hydroperoxy-10(E)-octadec-10-en-12-ynoic acid. Fe(II)-lipoxygenase does not convert the inhibitor and is not inactivated by 9-ODEYA. Fe(III)-lipoxygenase converts 12-ODEYA into 13-hydroperoxy-11(Z)-octadec-11-en-9-ynoic acid (34/66 R/S), 13-hydroperoxy11(E)-octadec-11-en-9-ynoic acid (36/64 R/S), 11-hydroperoxyoctadec-12-en-9-ynoic acid (11-HP-12-ODEYA, enantiomeric composition of 33/67), and 11-oxooctadec-12-en-9-ynoic acid (11-oxo-12-ODEYA) during the inactivation process. Also, Fe(II)-lipoxygenase is inactivated by 12-ODEYA. It converts the inhibitor into the same products as Fe(III)-lipoxygenase does, but two additional products are formed, viz. 13-oxo-11(E)-octadec-11-en-9-ynoic acid and 13-oxo-11(Z)-octadec-11-en-9-ynoic acid. The purified reaction products were tested for their lipoxygenase inhibitory activities. The oxo compounds, formed in the reaction of 9-ODEYA and 12-ODEYA, do not inhibit Fe(II)- or Fe(III)-lipoxygenase. The 9- and 13-hydroperoxide products that are formed from 9-ODEYA and 12-ODEYA, respectively, oxidize Fe(II)-lipoxygenase to its Fe(III) state and are weak lipoxygenase inhibitors. 11-HP-12-ODEYA is, however, the most powerful inhibitor and is able to oxidize Fe(II)-lipoxygenase to Fe(III)-lipoxygenase. 11-HP-12-ODEYA is converted into 11-oxo-12-ODEYA by Fe(III)-lipoxygenase. We propose a mechanism for the latter reaction in which Fe(III)-lipoxygenase abstracts the bisallylic hydrogen H-11 from 11-HP-12-ODEYA, yielding a hydroperoxyl radical which is subsequently cleaved into 11-oxo-ODEYA and a hydroxyl radical which may inactivate the enzyme.

Alkynes↗

Effect of dietary conjugated linoleic acid (CLA) on broiler performance, serum lipoprotein content, muscle fatty acid composition and meat quality during refrigerated storage.

1. A trial was conducted to investigate the effects of dietary conjugated linoleic acid (CLA) concentration on performance parameters, carcase composition, thiobarbituric acid reactive substances (TBARS) and fatty acid composition in leg and breast muscle and serum lipoprotein concentrations. 2. A total of 128 male chickens were allocated to 4 dietary treatments (0, 1, 2 and 3% CLA) and given a standard starter diet from d 1 to d 21 and a finisher diet from d 22 to d 42. Breast and leg muscles were stored at 4 degrees C for 1, 3 or 7 d. Fatty acid composition, TBARS and pH were determined in muscles. 3. Weight gain and feed conversion ratio were positively influenced by dietary CLA level. CLA isomer concentration in muscles increased linearly (P < 0.01) as dietary CLA increased. Addition of CLA to feeds significantly increased saturated fatty acid (SFA) and polyunsaturated fatty acid (PUFA) and decreased (P < 0.01) monounsaturated fatty acid (MUFA) in leg and breast tissues. 4. Muscle pH decreased with duration of refrigerated storage. TBARS values were significantly (P < 0.01) influenced by dietary CLA and storage time. CLA increased total cholesterol, LDL-cholesterol and HDL-cholesterol, but reduced triglycerides in the plasma of broilers.

Animal Feed↗

Vitamin E attenuates induction of elastase-like activity by tumor necrosis factor-alpha, cholestan-3 beta,5 alpha,6 beta-triol and linoleic acid in cultured endothelial cells.

Disturbances in arterial wall elastin metabolism appear to be important factors in atherosclerosis development. To evaluate this hypothesis, elastase-like activity was determined in cultured endothelial cells and their surrounding media after exposure to tumor necrosis factor-alpha (TNF), cholestan-3 beta,5 alpha,6 beta-triol (Triol) and linoleic acid (18:2). Significant increases in elastase-like activity both in the cells and in the media were observed when subconfluent endothelial cells were treated with 12 microM Triol, 500 U TNF/ml, or 90 microM 18:2, for 72 h in the presence of 5% calf serum. Even higher activities were measured when endothelial cells were seeded directly into media enriched with 18:2, TNF or Triol and treated for 72 h. Vitamin E supplementation (25 microM) attenuated elastase-like activity in cells and media, independent of treatment. These results suggest that elastase-like enzyme induction in endothelial cells may be involved in cellular perturbations induced by certain lipids and cytokines. Vitamin E may provide a protective function by preventing the induction of elastolytic enzymes. This may have implications in elastin metabolism and atherosclerosis.

Animals↗