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)

The aim of this study was to investigate whether a number of key haemostatic factors were altered when healthy young individuals were challenged with a fat load of physiological size contained within a meal composed of normal ingredients and whether this response was modified when the fatty acid composition of the meal was altered radically. Eight healthy male volunteers each randomly consumed four meals which were identical in terms of gross nutritional content (41% of energy provided as fat, 17% as protein and 42% as carbohydrate) but which differed in fatty acid composition. To reduce the possible influence of fatty acid position within the triglyceride molecule on lipid absorption and subsequent metabolic effects, the structural integrity of 91% of fat (test triglycerides such as 1,3 distearoyl-2-oleoyl glycerol (S-O-S), trioleine (O-O-O), and 1,3 dilinoleoyl-2-oleoyl glycerol, (L-O-L)) in the meals was controlled so that the principal fatty acid in the sn-2 position was oleic acid (18:1n-9). Meals rich in either a test triglyceride or a control oil provided 44+/-6 g of fat. No significant alterations from fasted values of elevated plasma factor VII coagulant activity (FVIIc) or F1 + 2 were observed. FVIIA varied significantly over the postprandial time course; however, when expressed as a percentage of the fasting value, the FVIIa responses to O-O-O and L-O-L differed significantly but this was not evident when the absolute values were analysed. Similarly, no difference in plasma fibrinopeptide A (FPA) concentrations were evident. After all four meals, chylomicron contained proportionately more palmitic acid and generally less oleic acid than the ingested lipids. This study clearly demonstrates that postprandial haemostatic responses of young healthy individuals to a physiological fat load are minimal, (irrespective of triglyceride structure).
Atherosclerosis 1999 Jan
PMID:The effects of structurally defined triglycerides of differing fatty acid composition on postprandial haemostasis in young, healthy men. 992 May 16

Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) activities were measured in sera from 32 normolipidemic women and men consuming diets enriched in lauric, palmitic, or oleic acids. Serum CETP activity, measured as the rate of radiolabeled cholesteryl esters transferred from HDL toward serum apo B-containing lipoproteins, was higher with the palmitic acid diet (25.1+/-2.5%) than with the lauric acid (23.7+/-2.4%) and the oleic acid (24.0+/-2.7%) diets (P = 0.0028 and 0.0283, respectively). CETP mass concentrations, as measured with an enzyme-linked immunosorbent assay were increased after the lauric acid diet (2.57+/-0.63 mg/l) and the palmitic acid diet (2.49+/-0.64 mg/l) as compared with the oleic acid diet (2.34+/-0.45 mg/l) (P = 0.0035 and 0.0249, respectively). In contrast with CETP, serum PLTP activity, as measured as the rate of radiolabeled phosphatidylcholine transferred from liposomes toward serum HDL, was significantly higher with the lauric acid diet (23.5+/2.6%) than with the palmitic acid diet (22.5+/-2.5%) (P = 0.0013), while no significant differences were noted when comparing the saturated diets versus the oleic acid diet (23.0+/-2.3%). No significant alterations in the mean apparent diameter of LDL, and in the relative proportions of individual HDL subpopulations were observed from one dietary period to another. Nevertheless, lipid transfer activities correlated significantly with the relative abundance of HDL2b, HDL2a, HDL3b, and HDL3c, with opposite tendencies being observed for cholesteryl ester transfer and phospholipid transfer activities. In general, serum CETP activity correlated negatively with HDL cholesterol, but positively with triglyceride concentrations after the dietary interventions, and the relations with serum lipids were just the opposite for PLTP activity. In addition, CETP and PLTP activities correlated negatively when subjects consumed the standardized diets (P < 0.05 in all cases), but not when subjects consumed their habitual diet. It is concluded that serum lipid transfer activities in normolipidemic subjects can be significantly affected by the fatty acid content of the diet, with differential effects on CETP and PLTP activities.
Atherosclerosis 1999 Feb
PMID:Variations in serum cholesteryl ester transfer and phospholipid transfer activities in healthy women and men consuming diets enriched in lauric, palmitic or oleic acids. 1003 Mar 91

Lysophosphatidylcholine (LPC) is present in oxidized low density lipoprotein (oxLDL), which is implicated in atherosclerosis. Antibodies to cardiolipin (aCL) and oxLDL (aoxLDL) have been shown to crossreact. LPC is formed by hydrolysis of phosphatidylcholine (PC) in LDL and cell membranes, induced by phospholipase A2 or by oxidation. We here demonstrate the presence of enhanced antibody levels to LPC in 184 patients with SLE as compared to 85 healthy, age-matched controls. The antibody reactivity to LPC was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only the saturated fatty acid palmitic acid showed equivalent antibody levels as LPC containing unsaturated fatty acids. aPC were significantly lower as compared to aLPC, indicating that hydrolysis of PC at the sn-2 position increases the antigenic potential of the molecule. Beta-glycoprotein 1 was a cofactor for aCL, but not for aoxLDL or aLPC, and the antigenicity of these compounds is therefore not directly related to beta2GP1. There was a close correlation between aoxLDL, aCL and aLPC and both LPC and oxLDL competitively inhibited aCL-binding to CL. LPC, oxLDL and CL thus display a common antigenic site, which could be formed by removal of a fatty acid at the sn-2 position, possibly due to the activity to phospholipase A2 and/or oxidation. This study indicates the potential role of LDL-oxidation and phospholipase A2 in SLE.
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PMID:Antibodies against lysophosphatidylcholine and oxidized LDL in patients with SLE. 1019 9

Serotonin (5HT) released from aggregating platelets at sites of vascular injury is a known mitogen for vascular endothelial cells. Recent studies have indicated that regenerating endothelial cells at sites of vessel wall injury may play a role in the development of restenosis by synthesizing and releasing growth factors for vascular smooth muscle cells, proliferation of which may result in the development of neointima. Diets rich in fish oils (omega-3 fatty acids) are associated with reduced risk of cardiovascular disease including atherosclerosis and restenosis. This study examined the effect of the omega-3 and other fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on 5HT induced endothelial cell proliferation. Among the fatty acids examined only EPA and DHA could reverse the mitogenic effect of 5HT on vascular endothelial cells, whereas oleic acid or palmitic acid did not have any effect. When added together, EPA and DHA potentiate each other in reversing the mitogenic effect of 5HT. EPA and DHA also inhibited the 5HT-induced increase in the 5HT2 receptor mRNA, without a change in the receptor density or affinity. This data suggests that one of the mechanisms by which omega-3 fatty acids may attenuate the development of atherosclerosis or restenosis is to inhibit the mitogen induced growth of vascular endothelial cells, which attenuates the release of growth factors for vascular smooth muscle cells.
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PMID:Serotonin-induced endothelial cell proliferation is blocked by omega-3 fatty acids. 1032 32

Diets rich in fish oils are associated with a reduced risk of cardiovascular disease including reduction of atherosclerosis and restenosis. We examined the effect of omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), major components of fish oils, on serotonin (5HT) stimulated vascular endothelial cells proliferation as a possible mechanism for this vascular protective effect. In this study we demonstrate that 5HT, a known mitogen for vascular endothelial cells, failed to stimulate proliferation of endothelial cells pre-incubated with EPA and DHA. This inhibitory effect was specific for omega-3 fatty acids only and not shared by other fatty acids like oleic acid (monounsaturated) or arachidonic acid (polyunsaturated) or palmitic acid (saturated). When endothelial cells were exposed to EPA and DHA in the ratio present in fish oils, EPA and DHA were shown to act synergistically in inhibiting the proliferative effect of 5HT. These results suggests that one of the mechanisms by which fish oils may confer vascular protective effect is by making the endothelial cells less responsive to mitogenic stimuli of growth factors such as 5HT that are released by aggregating platelets at sites of vascular injury. This inhibition of endothelial cell proliferation may account for the clinically observed effects of fish oil in attenuating the progression of atherosclerotic changes or neointimal proliferation following vascular injury.
Atherosclerosis 1999 Jul
PMID:Serotonin fails to induce proliferation of endothelial cells preloaded with eicosapentaenoic acid and docosahexaenoic acid. 1042 4

The changes in low density lipoprotein (LDL) composition and oxidizability after LDL-apheresis (LA) using dextran sulfate cellulose columns were evaluated in 12 hypercholesterolemic men (mean+/-S.D. total cholesterol (TC) 9.7+/-1.8 mmol/l). After 10-20 months on biweekly LA combined with simvastatin 40 mg per day immediate pre-apheresis levels of TC, LDL-cholesterol, and apolipoprotein B were decreased to 5.3+/-1.3 mmol/l, 3.3+/-1.2 mmol/l, and 1.6+/-0.4 g/l, respectively, whereas apheresis induced mean acute reductions of 61, 78, and 76%, respectively. Measurements of copper-induced LDL-oxidizability in vitro showed an increased resistance against oxidation after LA until day 3 post-treatment: lag time (min) (day 0 (before LA) versus day 1 (post-LA)) 112+/-27 versus 130+/-26 (P=0.001), maximal rate of diene production (nmol/min per mg LDL) 11.1+/-2.7 versus 9.1+/-2.1 (P=0.001), and time to maximal diene production (min) 186+/-39 versus 209+/-35 (P=0. 001). Analysis of the chemical composition of LDL revealed a 25% (P<0.001) reduced content of cholesteryl esters and a decrease of the cholesterol to protein ratio of 1.20+/-0.25 to 0.70+/-0.22 (P<0. 001) through the 3rd day post-LA. Linoleic acid and arachidonic acid content of LDL decreased 11 and 18%, respectively, at the expense of palmitic acid. Vitamin E levels (mg/l) were significantly lowered due to reduction of the lipoprotein pool by apheresis; however, vitamin E content of LDL did not change in the days after apheresis when expressed per g protein or per micromol linoleic acid. The changes in fatty acid pattern were strongly associated with changes in LDL-oxidizability indices (P</=0.01). Thus, LA effectively decreased LDL pool size, inducing the presence of less buoyant lipoproteins, which were less susceptible to in vitro oxidation. This was not explained by changes in vitamin E levels, but by short-term changes in the fatty acids composition.
Atherosclerosis 1999 Nov 01
PMID:The rebound of lipoproteins after LDL-apheresis. Effects on chemical composition and LDL-oxidizability. 1052 31

We have investigated the effect of fatty acids on the rate of apolipoprotein B (apo B) secretion by human hepatoma cells (Hep G2). When Hep G2 cells were maintained in tissue culture flasks oleic acid up to 0.4 mM increased apo B secretion in a dose-dependent manner, whereas increases in triacylglycerol (TG) were smaller and dose dependency was less evident. In the absence of oleic acid, apo B accumulating in the tissue culture medium was predominantly in lipoproteins of higher density than very low density lipoproteins (VLDL). However, when the rate of secretion was stimulated with oleic acid the apo B-containing lipoproteins became lower in density. We postulated that there was a high rate of lipolysis of newly secreted VLDL by Hep G2 cells, which would account both for the relatively smaller effect of oleic acid on TG as opposed to apo B accumulating in the culture medium and the predominance of apo B in lipoproteins of a higher density than VLDL, which became less evident when VLDL secretory rates were stimulated by oleic acid. To test this hypothesis, cultured Hep G2 cells were transferred to columns containing Cytodex beads, permitting their continuous perfusion with culture medium so that newly secreted VLDL did not remain in contact with the cells. Apo B recovered from the perfusate was largely in VLDL range lipoproteins and the TG measured in the perfusate indicated that the true secretory rate of TG-rich lipoproteins was substantially higher than had been reflected by TG accumulating in culture medium left in contact with cells. Apo B measured in the culture medium of Hep G2 cells may thus be a better reflection of VLDL secretion, even though it is contained in higher density lipoproteins due to removal of TG by lipolysis. The effects of saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA) on apo B (apo B) secretion by Hep G2 cells maintained in tissue culture flasks were next investigated. SFA (0.4 mM), with the exception of stearic acid (C18:0), increased apo B secretion. Lauric acid (C12:0) increased apo B secretion by 32%, myristic acid (C14:0) by 41% (P<0.005), palmitic acid (C16:0) by 154% (P<0.025), and arachidic acid (C20:0) by 186% (P<0.005). The effect of MUFA (0.4 mM) was to increase apo B secretion, oleic acid (C18:1) by 239% ((P<0.0005) and palmitoleic acid (C16: 1) by 125% (P<0.005). Of the PUFA investigated, linolenic acid (C18:3) (0.4 mM) did not have any significant effect on apo B secretion, whereas linoleic acid (C18:2) (0.4mM) arachidonic acid (C20:4) (0.1 mM) and eicosapentaenoic acid (C20:5) (0.1 mM) caused significant increases of 164, 171 and 171%, respectively (P<0.005). The fatty acids studied increased intracellular TG and cholesteryl ester concentrations to varying extents. The increase in intracellular TG produced by the different fatty acids correlated with the rate of apo B secretion (r=0.6; P<0.05). In this human hepatoma cell line, with the exception of the saturated fatty acids, the rate of secretion of apo B-containing lipoproteins does not follow the same pattern as changes in circulating low density lipoprotein (LDL) concentrations reported with dietary manipulation in man. If our findings reflect the in vivo situation, we suggest that whilst the dietary effects of SFA on serum LDL may in part be determined by the hepatic apo B secretory rate, the effects of MUFA and PUFA must be largely mediated through a catabolic effect rather than an effect on hepatic secretion. The marked increase in apo B secretion with the more highly polyunsaturated fatty acids, such as eicosapentaenoic acid, may also explain why they do not lower circulating LDL, despite reports of their apparently favourable effect on LDL-receptor mediated clearance.
Atherosclerosis 2000 Jun
PMID:The effects of fatty acids on apolipoprotein B secretion by human hepatoma cells (HEP G2). 1085 17

Earlier work has shown that increasing concentration of palmitic acid at the sn-2 position of a fat enhances the atherogenic properties of that fat. This effect has been observed with lard, tallow, cottonseed oil, and palm oil. In the experiment reported here, we have studied the atherogenic effects of four synthetic fats fed to rabbits as 58% (w/w) of the total fat (15%) (w/w) of a semipurified diet containing 0.05% cholesterol. The fats being tested were: 1,3-stearoyl-2-oleoylglycerol (SOS); 1,2-stearoyl-3-oleoylglycerol (SSO); 1,3-palmitoyl-2-oleoylglycerol (POP); and 1,2-palmitoyl-3-oleoylglycerol (PPO). After 20 wk on diet there were no differences among the groups in weight gain, liver weight, serum, or liver lipids. These data are consistent with our previous findings. There were significant differences in atherosclerosis. The most severe atherosclerosis was observed in group PPO and the least in groups SSO and POP. Severity of atherosclerosis was graded visually on a 0-4 scale. The average atherosclerosis [(aortic arch and thoracic aorta) divided by 2] was: SOS--1.35; SSO--0.97; POP--0.83; and PPO--1.80. Fecal fat excretion (an indicator of fat absorption) was higher in the two groups fed the stearic acid-rich fats and lower in groups fed the palmitic acid-rich fats. There were no differences in low density lipoprotein particle size. The results confirm previous findings concerning the increased atherogenicity of fats bearing palmitic acid at the sn-2 position. The mechanism underlying these observations is moot but may, in part, reflect greater absorption of the atherogenic fat.
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PMID:Cholesterol vehicle in experimental atherosclerosis. 23. Effects of specific synthetic triglycerides. 1090 23

Atherosclerosis is a major complication of type 2 diabetes. The pathogenesis of this complication is poorly understood, but it clearly involves production in the vascular wall of macrophage (Mo) lipoprotein lipase (LPL). Mo LPL is increased in human diabetes. Peripheral factors dysregulated in diabetes, including glucose and free fatty acids (FAs), may contribute to this alteration. We previously reported that high glucose stimulates LPL production in both J774 murine and human Mo. In the present study, we evaluated the direct effect of FAs on murine Mo LPL expression and examined the involvement of peroxisome proliferator-activated receptors (PPARs) in this effect. J774 Mo were cultured for 24 h with 0.2 mmol/l unsaturated FAs (arachidonic [AA], eicosapentaenoic [EPA], and linoleic acids [LA]) and monounsaturated (oleic acid [OA]) and saturated FAs (palmitic acid [PA] and stearic acid [SA]) bound to 2% bovine serum albumin. At the end of this incubation period, Mo LPL mRNA expression, immunoreactive mass, activity, and synthetic rate were measured. Incubation of J774 cells with LA, PA, and SA significantly increased Mo LPL mRNA expression. In contrast, exposure of these cells to AA and EPA dramatically decreased this parameter. All FAs, with the exception of EPA and OA, increased extra- and intracellular LPL immunoreactive mass and activity. Intracellular LPL mass and activity paralleled extracellular LPL mass and activity in all FA-treated cells. In Mo exposed to AA, LA, and PA, an increase in Mo LPL synthetic rate was observed. To evaluate the role of PPARs in the modulatory effect of FAs on Mo LPL gene expression, DNA binding assays were performed. Results of these experiments demonstrate an enhanced binding of nuclear proteins extracted from all FA-treated Mo to the peroxisome proliferator-response element (PPRE) consensus sequence of the LPL promoter. PA-, SA-, and OA-stimulated binding activity was effectively diminished by immunoprecipitation of the nuclear proteins with anti-PPAR-alpha antibodies. In contrast, anti-PPAR-gamma antibodies only significantly decreased AA-induced binding activity. Overall, these results provide the first evidence for a direct regulatory effect of FAs on Mo LPL and suggest a potential role of PPARs in the regulation of Mo LPL gene expression by FAs.
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PMID:Direct regulatory effect of fatty acids on macrophage lipoprotein lipase: potential role of PPARs. 1124 88

Male hamsters (30 per group) were fed five different semi-purified diets ad libitum. The diets, containing 30% of energy (en%) as fat, differed in their dietary fat composition (specified fatty acids exchanged at 10 en%) and were fed for 4 weeks. The five fatty acids compared in mixed triglycerides were elaidic acid (C18:1 9t), vaccenic acid (C18:1 11t), their cis-counterpart oleic acid (C18:1 9c), medium-chain fatty acids (MCFA; C8:0 and C10:0), and palmitic acid (C16:0). Compared with oleic acid, dietary MCFA and palmitic acid tended to increase blood cholesterol levels in the hamsters. The effect of elaidic and vaccenic acid on blood cholesterol did not differ from that of oleic acid. When elaidic acid and vaccenic acids were compared directly, the ratio of LDL/HDL-cholesterol in plasma was significantly higher in hamsters fed vaccenic acid than in those fed elaidic acid, and elaidic acid was incorporated at low levels, but more efficiently than vaccenic acid at the sn-2 position of platelet phospholipids. Biological consequences of this low incorporation are considered unlikely as levels of arachidonic acid (C20:4 n-6) and docosohexaenoic acid (C22:6 n-3) in the platelet phospholipids of all dietary groups did not differ. With respect to the effect on the LDL/HDL-cholesterol ratio, elaidic acid may be preferable to vaccenic acid. We conclude that this animal study does not provide evidence for the suggestion, based on epidemiological observations, that elaidic acid would be more detrimental to cardiovascular risk than vaccenic acid.
Atherosclerosis 2001 Jul
PMID:Effect of dietary elaidic versus vaccenic acid on blood and liver lipids in the hamster. 1142 1


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