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)

The ultrastructural effects of a single brief intra-arterial infusion of palmitic, linoleic and acetoacetic acid on the arterial endothelium of the rat were investigated, and the following results obtained: (1) Palmitic acid, infused at a concentration of 4 mM/l, damaged the arterial lining by producing large cytoplasmic clefts and occasional blebbing and lysis of the endothelial cells. By contrast, linoleic acid, infused at the same concentration, had no damaging effects on arterial endothelium. (2) Acetoacetic acid damaged the arterial wall when infused at concentrations of 0.2 mM/l or higher by inducing extreme swelling and loss of cristae of the mitochondria in arterial endothelium and myocytes. The above results raise the possibility that (a) high saturated fatty acid diets may promote atherosclerosis not only by inducing hypercholesterolemia but also by injuring the arterial lining, and (b) diabetes may promote atherosclerosis not only by inducing hyperlipemia but also by damaging the arterial wall during periods of uncontrolled ketoacidosis.
Atherosclerosis
PMID:Arterial effects of palmitic, linoleic and acetoacetic acid. 722 70

The aortic endothelium of rabbits, fed an atherogenic diet, has been studied by electron microscopy and by analysis of the distribution of intravenously injected, labeled, LDL and VLDL in plasma and aortic wall. It has been proposed that, in experimental hypercholesterolemia, when the receptor mechanism of lipoprotein uptake is saturated, a receptor-independent endocytosis plays the main role in the uptake of lipoproteins particles by endothelial cells. It has been established that, during the early stages of experimental hypercholesterolemia and atherosclerosis, there was an increase in the number of vesicles of 100-250 A in diameter, even up to 750 A, in the endothelial cells. Thus, it seems probable that there is transendothelial passage, not only of LDL, but also of particles like VLDL. Furthermore, the electron microscopy data have shown the possible formation of transedothelial canals by fusion of 3-4 vesicles. As hypercholesterolemia and atherosclerosis increase, the transport of lipoproteins occurs mostly through intercellular spaces and impaired endothelial regions. The intravenous administration to rabbits of LDL and VLDL, labeled with 14C-palmitic acid in their outer shell (phospholipids) and core (triglycerides + esters of cholesterol), has revealed a preferential penetration of small lipoprotein particles and of phospholipid-rich triglyceride-poor residues, both in normal and atherosclerotic aortas.
 ...
PMID:Functional characteristics of the endothelium on the dynamics of experimental atherosclerosis. 732 20

The fatty acid composition of the cholesteryl esters in serum was measured in 7- and 8-year-old boys in groups from 16 countries. The ratio of esterified cholesterol: total cholesterol was also measured. All sample collections and analyses were carried out under standardized conditions. The proportion of palmitic acid in the cholesteryl esters was high in the groups from Asia and Africa (0.17-0.26) compared with that in the groups from the U.S.A. and Europe (0.14-0.18). The proportion of linoleic acid in the cholesteryl esters was low in the groups from Asia and Africa (0.39-0.48) and high in the groups from the U.S.A. and Europe (0.45-0.58). The proportion of oleic acid, arachidonic acid, palmitoleic acid and stearic acid showed little variation between the groups. The proportion of linoleic acid in the cholesteryl esters was positively correlated with the concentration of total cholesterol (r = 0.75, n = 26, P < 0.005).
Atherosclerosis 1980 Dec
PMID:Fatty acid composition of cholesteryl esters in serum in boys from 16 developing and developed countries. 745 4

Binding of fibrinogen to platelets washed from the blood of patients with hypercholesterolemia and hypertriglyceridemia (n = 25) and control donors (n = 12) was compared. In addition, the content of platelet glycoprotein IIb was determined by radioimmunoassay. Fibrinogen was bound in significantly higher amounts (P < 0.02) to hyperlipidaemic platelets activated by ADP than to control ones (107,112 +/- 16,371 and 45,612 +/- 6495 molecules per platelet, respectively). The mean content of GPIIb was the same in hyperlipidaemic and in control platelets (2.06 +/- 0.16 and 1.94 +/- 0.21 micrograms/10(8) platelets, respectively). The amount of fibrinogen bound to the activated hyperlipidaemic platelets showed a positive correlation with total plasma cholesterol and LDL (r = 0.45 and 0.47, respectively) whereas a negative correlation with plasma HDL was found (r = -0.50). The increased expression of fibrinogen binding sites similar to that of hyperlipidaemic platelets could be produced by preincubation of normal platelets with palmitic acid. This was evidenced by a significant increase of fibrinogen binding sites in control platelets. This suggests that either palmitoylation of the receptor or microenvironment changes in the membrane lipid bilayer may be responsible for the enhanced platelet receptor capacity to bind fibrinogen.
Atherosclerosis 1993 Oct
PMID:Increased platelet-fibrinogen interaction in patients with hypercholesterolemia and hypertriglyceridemia. 828 Jan 81

The effect of dietary hydrogenated corn oil (trans-octadecenoate-rich oil) on plasma cholesterol and triglyceride concentrations was compared with dietary palmitic acid in hamsters given a cholesterol-rich diet. The addition of dietary palmitic acid and hydrogenated corn oil accelerated the increase in plasma VLDL- and LDL-cholesterol levels and plasma triglyceride level induced by dietary cholesterol loading. Dietary cholesterol, palmitic acid and hydrogenated corn oil showed no effect on plasma HDL-cholesterol concentration. A decrease in hepatic LDL receptor activity was seen in animals fed a diet supplemented with cholesterol in combination with palmitic acid or hydrogenated corn oil in comparison with animals fed a diet supplemented with cholesterol alone. Hydrogenated corn oil (trans-octadecenoate-rich oil) appears to potentiate the effect of dietary cholesterol in elevating the plasma VLDL- and LDL-cholesterol levels through the suppression of hepatic LDL receptor activity. trans-Octadecenoate in dietary hydrogenated corn oil may be as atherogenic as dietary palmitic acid due to a suppression of hepatic LDL receptors in the presence of dietary cholesterol loading.
Atherosclerosis 1993 Feb
PMID:Effect of dietary hydrogenated corn oil (trans-octadecenoate rich oil) on plasma and hepatic cholesterol metabolism in the hamster. 846 Oct 65

A study was made of the fatty acid composition of the total phospholipid fraction of human coronary arteries in 30 cases of sudden cardiac death due to ischaemic heart disease (aged 40 +/- 5 years, mean +/- S.D.) and in 29 controls (mostly traffic accident victims, aged 45 +/- 6 years). The coronary arteries from cases of sudden cardiac death showed more atherosclerotic lesions than those of controls (P < 0.001). The percentages of palmitic acid (16:0) and linoleic acid (18:2(n-6)) were significantly higher and the percentage of arachidonic acid (20:4(n-6)) and of all the other major polyunsaturated fatty acids, both n-6 and n-3, was significantly lower in cases of sudden cardiac death than in controls. In conclusion, this study showed increased percentages of saturated and reduced percentages of polyunsaturated fatty acids, except linoleic acid, in total phospholipids of human coronary arteries in cases of sudden cardiac death. The results suggest an impaired metabolism of linoleic acid, possibly due to a decreased delta-6-desaturase activity in the coronary artery wall in cases of sudden cardiac death.
Atherosclerosis 1993 Mar
PMID:Fatty acid composition in total phospholipids of human coronary arteries in sudden cardiac death. 850 47

We studied the effects of addition of physiological concentrations (0.5 mM) of fatty acids i.e., palmitic (16:0), stearic (18:0), oleic (18:1) and linoleic acid (18:2) on lipoprotein secretion by polarized Caco-2 cells. With saturated fatty acids, secreted lipoproteins were at IDL/LDL density, 1.009 < d < 1.068 g/ml. The numbers of secreted lipoproteins, expressed as secreted apolipoprotein (apo) B, were comparable to control without fatty acid (palmitic acid, 551 +/- 185; stearic acid, 629 +/- 304 and control, 504 +/- 176 ng apo B/4.7 cm2 filter). With unsaturated fatty acids, apo B containing lipoproteins were secreted at chylomicron/VLDL density (d < 1.006 g/ml). Oleic acid caused a two-fold higher secretion of apo B than control (1058 +/- 87 vs. 504 +/- 176 ng/4.7 cm2 filter, P < 0.001). The increase in apo B secretion was attributed to a specific increase in apo B-48. Unsaturated fatty acid caused a two-fold higher secretion of triglyceride than saturated fatty acids but incorporation of newly synthesized lipid into the secreted lipoproteins, measured by incorporation of a fatty acid marker, was 10- to 20-fold higher, indicating preferential translocation of unsaturated triglycerides into lipoproteins. Mixtures rich in either polyunsaturated, monounsaturated, or saturated fatty acids, resembling nutritional fat and oils, were capable of a two-fold stimulation of secretion of apo B containing triglyceride-rich lipoproteins. The triglyceride/apo B ratio in the basolateral medium was higher with the monounsaturated 'olive oil' mixture (12 250 +/- 2000 mol/mol) than with the polyunsaturated 'corn oil' mixture (7830 +/- 2480 mol/mol) and incorporation of newly synthesized lipid into the secreted lipoproteins was 1.5-fold higher as well. In conclusion, unsaturated fatty acids were most potent in stimulating the secretion of apo B by specifically increasing apo B-48 secretion. Unsaturated triglycerides, that contain mainly oleic acid, were more efficiently incorporated into lipoproteins than saturated triglycerides, suggesting preferential translocation by microsomal triglyceride transfer protein.
Atherosclerosis 1996 Mar
PMID:Effects of saturated, mono-, and polyunsaturated fatty acids on the secretion of apo B containing lipoproteins by Caco-2 cells. 867 19

Dietary saturated fatty acids are implicated as a risk factor for atherosclerosis. The conversion of the major dietary saturated fatty acids stearic acid (18:0) and palmitic acid (16:0) to monounsaturated fatty acids in whole plasma and lipoprotein fractions is reported for seven healthy adult humans over 6 d using [U-13C]stearic acid (18:0*) and [U-13C]palmitic acid (16:0*) and high-precision mass spectrometry. A tracer dose (28-32 mg) of 18:0* or 16:0* was loaded into an emulsion and orally administered before breakfast. Serial blood samples were collected on day 1 and fasting blood was drawn daily until day 7. Overall conversion of 18:0 to 18:1 was approximately 14%, whereas that of 18:0 to 16:0 was approximately 2% in plasma up to 144 h. Conversion of 16:0 to 16:1 was < 2%, whereas conversion of 16:0 to 18:0 was approximately 6%. No other fatty acid metabolites were detected for 18:0* or 16:0*. The conversion products were observed mainly in chylomicrons and very-low-density lipoproteins, indicating that the intestine and liver have comparable roles in desaturating 18:0 and 16:0. Overall, these data indicate that dietary 18:0 desaturation is severalfold greater than 16:0 desaturation. The low level (14%) of 18:0 desaturation in omnivorous adults may have little influence on blood lipid profiles relevant to atherosclerosis risk.
 ...
PMID:Desaturation and interconversion of dietary stearic and palmitic acids in human plasma and lipoproteins. 902 30

Several studies showed a diminished production of the endothelium-derived relaxing factor nitric oxide (NO) in the early stage of atherosclerosis. The inhibition of NO-production seems to be mediated by lipoproteins, especially oxidized low-density lipoproteins (ox-LDL). There is some evidence, that the interactions of lipoproteins and NO are associated with the phospholipid fraction of lipoproteins. Since fatty acids have different atherogenic properties-depending on chain length, degree of saturation and steric configuration-, we investigated the effect of fatty acids on endothelial NO-production. Human umbilical vein endothelial cells were incubated with palmitic acid and stearic acid in different concentrations in culture medium enriched with serum albumin for five hours. After that, NO-production was stimulated by calcium-ionophore A23187. NO-production was determined by a bioassay method using RFL-6 cells followed by radioimmunological determination of cGMP. NO-production stimulated by calcium-ionophore A23187(100%) was decreased by palmitic acid (10, 50, 100 microM) to 79 +/- 12%; 63 +/- 10% and 53 +/- 14%. In contrast, incubation with stearic acid (10, 50 and 100 microM) had no effect on A23187-stimulated NO-production (94 +/- 11%; 93 +/- 11%; 104 +/- 15%). Thus, palmitic acid but not stearic acid dose-dependently inhibited NO-release by endothelial cells. These different actions parallel the differing atherogenic potential of the two fatty acids.
 ...
PMID:Palmitic acid but not stearic acid inhibits NO-production in endothelial cells. 928 52

Lysophosphatidylcholine (LPC) is formed by hydrolysis of PC in low density lipoprotein (LDL) and cell membranes by phospholipase A2 or by oxidation. Oxidized (ox) LDL activates endothelial cells, an effect mimicked by LPC. oxLDL also has the capacity to activate T and B cells, and antibody titers to oxLDL are related to the degree of atherosclerosis. The antigen in oxLDL responsible for its immune-stimulatory capacity is not well characterized, and we hypothesized that LPC was involved. We demonstrate herein the presence of antibodies against LPC, both of the IgG and IgM isotype, in 210 healthy individuals. This antibody reactivity was not specifically related to oxidation of the fatty acid moiety in LPC, since LPC containing only palmitic acid showed antibody titers equivalent to those of LPC containing unsaturated fatty acids. Antibody titers to PC were low compared with LPC, and hydrolysis of PC at the sn-2 position is thus essential for immune reactivity. There was a close correlation between anti-oxLDL and anti-LPC antibodies. Furthermore, LPC competitively inhibited anti-oxLDL reactivity, which indicates that LPC may explain a significant part of the immune-stimulatory properties of oxLDL. LPC, being a lipid, is not likely to be an antigen itself. Instead, LPC could form immunogenic complexes with peptides, which may induce and potentiate immune reactions in the vessel wall. This study adds to the evidence that LPC is an important component of oxLDL and emphasizes the potential role of phospholipase A2 in atherosclerosis.
 ...
PMID:Lysophosphatidylcholine is involved in the antigenicity of oxidized LDL. 955 69


<< Previous 1 2 3 4 5 6 7 8 9 Next >>