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 effects of C1-719 on plasma lipid and lipoprotein concentrations have been examined in four patients with endogenous hypertriglyceridaemia maintained on an isocaloric diet for a period of 6 months. During therapy (400 mg/day) the mean plasma triglyceride and cholesterol concentrations were reduced by 35% and 15% respectively, while the administration of 800 mg/day reduced these by 49% and 31%. This hypolipidaemic effect was due to a reduction in the circulating level of very low density lipoproteins (VLDL) without a change in their composition. Before treatment the plasma VLDL triglyceride turnover, and FFA flux, were higher than that of normal subjects maintained on a similar diet. The plasma VLDL B-apoprotein turnover was similarly higher than in the controls. Administration of C1-719 decreased the plasma VLDL triglyceride turnover, FFA flux and VLDL B-approtein turnover. The drug reduced the insulin response following a glucose load with some decrease in glucose levels. The results suggest that the increase in plasma triglyceride concentration in patients with endogenous hypertriglyceridaemia is due to increased production of plasma VLDL triglyceride and its apoptein associated with an enhanced supply of FFA for hepatic triglyceride synthesis. C1-719 exerts a hypolipidaemic effect through a reduction of VLDL production, consequent upon inhibition of lipolysis as well as decreased synthesis of the apoprotein carrier. These effects could in part be explained by an improvement in peripheral tissue responsiveness to insulin and decreased exposure of the liver to high levels of insulin. However, a direct effect of the drug on adipose tissue and liver metabolism has to be considered.
Atherosclerosis
PMID:Transport kinetics of plasma free fatty acid, very low density lipoprotein triglycerides and apoprotein in patients with endogenous hypertriglyceridaemia: effects of 2,2-dimethyl, 5(2, 5-xylyoxy) valeric acid therapy. 18 85

The fatty acid patterns of serum triglycerides and FFA in SHR and in normotensive controls aged 4, 8 and 26 weeks were estimated by gas-liquid chromatography. In serum triglycerides of SHR, the percentage of linoleic acid (C18:2) was lower and the content of arachidonic acid (C20:4) higher than in age-matched control animals. A continuous increase in palmitic (C16) and linoleic acids as well as a decrease in arachidonic acid has been found with advancing age, the most striking differences existing between 4- and 8-week-old animals, i.e. before onset of arterial hypertension in SHR. In the pre-hypertensive stage, the percentage of arachidonic acid was about 3 times as high as in later stages in SHR. This gradation was, however, even more pronounced in normotensive control rats. The C18:2/C20:4-ratio of triglycerides was lower in SHR but increased with age in both groups reaching a 5--8-fold level. Similar behavior of the FFA fatty acid pattern was less marked. Alterations in levels of linoleic and arachidonic acids are of interest because of their pathogenic role as precursors of prostaglandins in the development of genetically spontaneous hypertension in rats. The results are discussed in connection with the hypotensive effect of a linoleic acid-rich diet recently reported in hypertensive rats.
Atherosclerosis 1979 Jun
PMID:The fatty acid pattern of triglycerides and FFA in serum of spontaneously hypertensive rats (SHR). 47 80

Arginine-induced insulin secretion was evaluated in 13 patients with endogenous hypertriglyceridemia (Fredrickson's Type IV) before and after a two-month period of Clofibrate therapy. Clofibrate reduced triglyceride, cholesterol and FFA levels by 68, 28 and 15% respectively and provoked a significant reduction in arginine-induced insulin secretion without modifying glucose response. Arginine-induced insulin secretion was also studied in 11 normal subjects during saline and intralipid infusions. Glucose and insulin basal values, and glucose and insulin response to arginine infusion were not influenced by Intralipid infusion in these controls. These results confirm that clofibrate reduces insulin secretion thereby contributing to decreased serum triglyceride levels.
Atherosclerosis
PMID:Effects of clofibrate treatment on arginine-induced insulin secretion in endogenous hypertriglyceridemia. 100 8

Hypertriglyceridemic (HTG) serum, lipolyzed in vitro by purified bovine milk lipoprotein lipase, was found to be cytotoxic to cultured macrophages. Surviving macrophages contained numerous lipid inclusions similar to those found in foam cells. Individual lipoprotein fractions isolated from the lipolyzed HTG serum, including HDL, were also cytotoxic. Lipolysis of isolated lipoprotein fractions (either HTG or normal) allowed localization of cytotoxicity to postlipolysis remnant VLDL and chylomicron particles. The presence of a critical concentration of HDL in either the lipolysis mixture or the culture dishes inhibited the cytotoxicity. Below this critical concentration HDL itself became cytotoxic, producing lipid inclusions in surviving macrophages. The lipid fraction of the cytotoxic remnants contained the cytotoxic factor(s); neither FFA nor lysolecithin alone could account for this cytotoxicity. Postprandial lipemic sera from subjects with a brisk chylomicron response, when lipolyzed in vitro, were cytotoxic to cultured macrophages; neither fasted sera from these subjects, nor postprandial sera from normolipidemic subjects with a normal chylomicron response, were cytotoxic. Postheparin (in vivo lipolyzed) serum and its isolated lipoprotein fractions obtained 30 min after heparin injection in subjects with HTG were shown to be cytotoxic to macrophages; by 60 min most of the cytotoxicity had disappeared. The postprandial and postheparin observations support an in vivo significance for remnant-associated cytotoxicity. We hypothesize that cytotoxic remnants of lipolyzed VLDL and chylomicrons may be one of the major atherogenic lipoproteins. Further, we suggest that inhibition of the cytotoxicity of these remnants may be one important way that HDL prevents atherosclerosis.
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PMID:Lipolytic surface remnants of triglyceride-rich lipoproteins are cytotoxic to macrophages but not in the presence of high density lipoprotein. A possible mechanism of atherogenesis? 270 36

With the advent of nocturnal intragastric feeding which protects against acute metabolic complications and promotes growth, patients with glycogen storage disease type I are attracting less attention. However, several biochemical alterations persist and suggest that the long-term risk of atherosclerotic heart disease remains high. Persisting hypertriglyceridemia and hypercholesterolemia were found in seven glycogen storage disease type I subjects, six of them following 5-6 yr of nocturnal intragastric feeding. When compared to ten age-matched controls, the patients showed significantly (P less than 0.001) higher low density lipoprotein cholesterol (LDL-C) (247.7 +/- 46.8 vs. 115.3 +/- 5.0 mg/dl) and lower high density lipoprotein cholesterol (HDL-C) (26.4 +/- 3.4 vs. 55.8 +/- 2.9 mg/dl). Triglyceride (TG) enrichment with cholesteryl ester depletion characterized the lipoprotein classes. The diameters of very low density lipoproteins (VLDL) and LDL were larger, while that of HDL was smaller and consistent with the predominance of the HDL3 subclass and a lower apoA-I/apoA-II ratio. The raised levels of TG appeared attributable not only to the well-described lipogenesis, but also to impaired catabolism of fat, as evidenced by the significantly (P less than 0.001) decreased activity of both peripheral lipoprotein lipase (3.17 +/- 0.43 vs. 14.15 +/- 0.50 mumol FFA.ml-1.hr-1) and hepatic lipase (1.88 +/- 0.30 vs. 4.83 +/- 0.90). This may well explain the high concentration of intermediate density lipoprotein (IDL) and the impaired conversion of HDL3 to HDL2. Low apoC-II/apoC-III1 could be related to defective lipoprotein lipase activity. These data suggest that glycogen storage disease type I patients on nocturnal intragastric feeding remain at risk for atherosclerosis and its complications.
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PMID:Circulating lipids and lipoproteins in glycogen storage disease type I with nocturnal intragastric feeding. 313 Apr 54

Motor car racing is representative of concentrative sporting activities, as well as instructive for mental-concentrative and psycho-emotional stress, which predominates with lower intensity, but longer duration in occupational work of today. A group of 20 car racing drivers was investigated both during car races (Formula Ford and Renault-5-Cup) and during progressive bicycle ergometry in the laboratory. Heart rate during car racing reached a mean level of 174.3 +/- 14.1 min-1 (mean +/- SD), corresponding to 90% of the maximal heart rate achieved at the end of exhaustive ergometry (n = 12). Catecholamine excretion in urine (adrenaline + noradrenaline) on average was 252.3 +/- 77.9 ng min-1 during car racing and 121.9 +/- 37.3 ng min-1 during exhaustive ergometry (n = 10). Most of the other metabolic parameters determined in blood (lactate, glucose, FFA = free fatty acids, plasma protein, insulin, HGH = human growth hormone) also showed significant differences between car racing and bicycle ergometry (n = 20). Therefore it is possible to distinguish between psychical and physical strain and the quantify their specific level. Especially blood lactate can be considered as a metabolic indicator of physical strain and FFA of psycho-emotional strain. Furthermore, significant negative correlations could be found between heart rate, FFA level, and catecholamine excretion during car racing and some measures of physical fitness determined on the bicycle ergometer (n = 12 or 10). This suggests a reduced cardiocirculatory and metabolic strain reaction in response to psychical stress situations with increased fitness. Moreover, HDL (high density lipoprotein) was found increased and oral glucose tolerance test was improved with elevated physical fitness (n = 20, respectively 16). From the results of this study it can be concluded that physical activity counteracts atherosclerosis and CHD (coronary heart disease), which are promoted by psycho-emotional and psycho-social stress.
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PMID:Heart rate, metabolic and hormonal responses to maximal psycho-emotional and physical stress in motor car racing drivers. 331 41

Low density lipoprotein (LDL) rich in oleic acid (designated FFA-rich LDL) was produced by the reconstitution technique. FFA-rich LDL, like acetyl LDL, moved faster than native LDL in agarose gel electrophoresis. While FFA-rich LDL was observed to degrade far less than natural LDL in lymphocytes, its degradation in monocyte-derived macrophages was three times higher than that of natural LDL or LDL reconstituted without the addition of oleic acid. A competitive study showed that the catabolism of FFA-rich LDL in macrophages may be influenced by systems other than the acetyl LDL receptor.
Atherosclerosis 1987 Jul
PMID:Enhanced degradation of low density lipoprotein in human monocyte-derived macrophages associated with an increase in its free fatty acid content. 363 46

In short-term experiments, healthy fasting persons were given a basic dose of 0.5 g of ethanol/kg body weight, followed by hourly maintenance doses of 0.15 g of ethanol/kg body weight. After 10 h there was a significant increase of triglycerides in the VLDL, LDL, and HDL, the main rise (from 42 to 92 mg/dl) being found in the VLDL triglycerides. Other subjects, who received nourishment isocaloric with ethanol, likewise showed a significant rise of triglycerides in all lipoprotein fractions. Chylomicron triglycerides increased from 9.3 to 35.5 mg/dl. There was no significant change in postheparin HTGL, but postheparin LPL activity decreased after 10 h from 17.9 to 12.2 mmol FFA/ml/h in the fasting subjects, and from 28.5 to 10.2 mmol/FFA/ml/h in the persons receiving food. In long-term experiments after 4 weeks of 70 - 80 g of ethanol and isocaloric food daily, triglycerides increased, especially in the VLDL (from 50 to 82 mg/dl). The increase in the HDL, however, was also significant. After 4 weeks of ethanol, the chylomicron triglycerides in the plasma of the fasting subjects reached a value of 29.3 mg/100 ml, LDL cholesterol decreased, and HDL cholesterol increased. After 4 weeks of ethanol there was an increase in the lipoprotein lipase of the adipose tissue.
Atherosclerosis 1985 Nov
PMID:Lipoprotein fractions, lipoprotein lipase and hepatic triglyceride lipase during short-term and long-term uptake of ethanol in healthy subjects. 408 59

The fatty acid compositions of 4 serum lipid fractions were analysed from 244 randomly selected 30-59-year-old Finnish men from 4 areas involved in a population survey ('Mini-Finland') in 1979-80. Men in eastern Finland had significantly lower mean percentages of linoleate (18:2) in CE, TG, FFA and PL (45.1, 10.3, 9.3 and 18.8%, respectively) than men in the western part of the country (48.4, 12.5, 10.6 and 20.2%, respectively). Very low values of 18:2 were encountered in the North Karelian community of Ilomantsi, especially in men aged 50-59 (40.9, 8.0, 7.5 and 16.8%, respectively). The percentage of alpha-linolenate tended also to be lower and those of saturated and monounsaturated fatty acids higher in the east, but there were no or only inconsistent differences in the contents of the prostaglandin precursors dihomo-gamma-linolenate, arachidonate and eicosapentaenoate. Eighteen men were studied in November and the following April. Only minor changes in the mean composition of serum fatty acids took place during this period and the correlation coefficients between the percentages of 18:2 recorded at the two time points ranged from 0.70 to 0.81. The low concentrations of 18:2 in serum lipids in Finnish men obviously reflect a low dietary P/S ratio and may contribute to the high prevalence of IHD in Finland and to its regional differences.
Atherosclerosis 1983 Nov
PMID:Serum fatty acids in Finnish men. 666 77

In rabbits kept on a diet containing 1 g/day cholesterol for 12 weeks, the nicotinic acid derivative sorbinicate displayed greater hypolipemic and antiatherogenic activity than an equidose of plain nicotinic acid at much lower and more constant plasma nicotinic acid levels. In normocholesterolemic rats, nicotinic acid given at a level of 300 mg/kg per dose for 3 weeks induced plasma FFA and triglyceride rebound and triglyceride accumulation in the liver and possibly in the heart (all parameters determined 24 h after the last dosing), whereas an equidose of sorbinicate was free from these effects, potentially the two most dangerous side effects of nicotinic acid. By modulating the bioavailability of nicotinic acid, sorbinicate maintains and in some cases enhances the pharmacological activity of the acid, avoiding at least some of its major side effects.
Atherosclerosis 1980 May
PMID:Comparative evaluation of some pharmacological properties and side effects of D-glucitol hexanicotinate (sorbinicate) and nicotinic acid correlated with the plasma concentration of nicotinic acid. 738 73


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