The changes of the composition of blood lipoproteins caused by menopause could also change the effect of hypolipidemic therapy. Using an experimental model we studied the changes of serum lipids and the effect of immediate or delayed treatment with simvastatin on atherosclerosis after surgical menopause. Female golden Syrian hamster aged 6 months were fed hypercholesterolemic diet during the whole study. Atherosclerotic changes in thoracic and abdominal aortas were assessed by stereomicroscopic method after 12 weeks. Four experimental groups were studied: sham-operated animals (n=5), ovariectomized animals (n=9), ovariectomized animals treated for 12 weeks (n=10), and ovariectomized animals treated 4 weeks after ovariectomy for 8 weeks (n=9). The dose of simvastatin was 10 mg/kg of body weight. After 12 weeks, ovariectomized animals had tenfold higher concentration of triglycerides in LDL fraction and significantly higher prevalence of atherosclerosis than animals without ovariectomy. Treatment with simvastatin substantially decreased the prevalence of atherosclerotic changes, but otherwise did not change individual serum lipids including LDL cholesterol. However, it improved proportions of pro- and antiatherogenic serum lipids mainly by the increase of HDL cholesterol. The timing of simvastatin treatment had no significant effect on atherosclerotic changes or lipid parameters. Simvastatin treatment partly prevented atherosclerotic changes induced by ovariectomy. This effect was not mediated by decrease of LDL cholesterol, but by increase in HDL cholesterol., J. Pitha ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
The subclass of triglyceride -rich lipoproteins - remnant -like particles (RLP) seems to be strong and independent risk factor for cardiovascular disease. We eva luated the role of RLP and other risk factors (RF) with sonographically measured intima - media thickness of carotid arteries (IMT CCA) in a cohort of Czech population including women defined according to the time after menopause. We investigated relation of IMT CCA to age, weight, central obesity, plasma lipids including remnant -like particles cholesterol (RLP -C) and triglycerides (RLP -TG) in 136 men and 160 women. Using multiple linear regression analysis, significant association between IMT CCA and RLP -C was found in women 1 -7 years after menopause. In the whole group of women, only age and fasting blood glucose were independently associated with IMT CCA. In men only age significantly correlated wit h IMT CCA. Significant decrease of all plasma lipids betwe en 1988 and 1996 in men was detected, while in women significant increase in triglycerides and no change in non -HDL cholesterol was observed. RLP -C was the strongest independent RF for atherosclerosis in postmenopausal women but its as sociation with IMT CC A was limited to several years after menopause. In conclusion, women changing reproductive status could be more sensitive to atherogenic impact of remnant lipoproteins., J. Piťha, J. Kovář, Z. Škodová, R. Cífková, P. Stávek, L. Červenka, T. Šejda, V. Lánská, R. Poledne., and Obsahuje bibliografii
Moderately elevated plasma/serum triglycerides (2 -10 m mol/l) signalize increased risk for cardiovascular disease or presence of non- alcoholic steatohepatitis. Extremely elevated triglycerides (more than 10 mmol/l) signalize increased risk for pancreatitis and lipemia retinalis. The concentration of triglycerides is regulated by many genetic and nongenetic factors. Extremely elevated triglycerides not provoked by nutritional factors, especially inappropriate alcohol intake are more likely to have a monogenic cause. On the contrary, mildly to moderately elevated triglycerides are often caused by polygenic disorders; these could be also associated with central obesity, insulin resistance, and diabetes mellitus. Concentration of triglycerides is also closely interconnected with presence of atherogenic remnant lipop roteins, impaired reverse cholesterol transport and more atherogenic small LDL particles. In general, there is tight association between triglycerides and many other metabolic factors including intermediate products of lipoprotein metabolism which are freq uently atherogenic. Therefore, reliable evaluation of the independent role of triglycerides especially in atherosclerosis and cardiovascular disease is difficult. In individual cases values of HDL cholesterol, non -HDL cholesterol (total minus HDL cholester ol), non -HDL/nonLDL cholesterol (total minus HDL minus LDL cholesterol, especially in nonfasting status), atherogenic index of plasma and/or apolipoprotein B could help in decisions regarding a ggressiv eness of treatment., J. Piťha, J. Kovář, T. Blahová., and Obsahuje bibliografii
The review aims to summarize current knowledge on the effects of moderate alcohol consumption ( 1 standard drink a day for women; 2 drinks a day for men) on triglyceride concentration in circulation. Current evidence suggests that the relationship between alcohol consumption and triglyceridemia is J -shaped. Triglyceridemia is lowest in subjects who drink 10 -20 g/alcohol a day. Such a J -shaped association is comparable with that described for the relationship between alcohol and cardiovascular risk. On the contrary, alcohol taken with a meal increases and prolongs postprandi al triglyceridemia. Such effects of alcohol consumption may be at least partially explained by the effects of ethanol on lipoprotein lipase (LPL) activity. Long -term moderate alcohol consumption increases LPL activity, which may explain its TG -lowering effect. On the other hand, LPL activity is acutely downregulated by ethanol, which explains increased postprandial triglyceridemia., J. Kovář, K. Zemánková., and Obsahuje bibliografii
Cholesterol 7α-hydroxylase (CYP7A1), the key regulatory enzyme of bile acid synthesis, displays a pronounced diurnal variation. To better understand the regulation of CYP7A1 activity, three daylong examinations were carried out in 12 healthy men. The concentrations of 7α-hydroxycholest-4-en-3-one (C4), a surrogate marker of CYP7A1 activity, bile acids (BA), insulin, glucose, nonesterified fatty acids, triglycerides, and cholesterol were measured in serum in 90-min intervals from 7 AM till 10 PM. To lower and to increase BA concentration during the study, the subjects received cholestyramine and chenodeoxycholic acid (CDCA), respectively, in two examinations. No drug was used in the control examination. There was a pronounced diurnal variation of C4 concentration with a peak around 1 PM in most of the subjects. The area under the curve (AUC) of C4 concentration was five times higher and three times lower when subjects were treated with cholestyramine and CDCA, respectively. No relationship was found between AUC of C4 and AUC of BA concentration, but AUC of C4 correlated positively with that of insulin. Moreover, short-term treatment with cholestyramine resulted in about 10 % suppression of glycemia throughout the day. Our results suggest that insulin is involved in the regulation of diurnal variation of CYP7A1 activity in humans., J. Kovář ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
To determine whether a short-term change in dietary habits affects postprandial lipemia in men and women in the same way, postprandial triglyceridemia was measured in age- and BMI-matched young healthy men and women after two weeks on the self-selected low-fat low-cholesterol (LF) diet and after another two weeks on the self-selected high-fat high-cholesterol (HF) diet. After a standardized challenge meal (1.4 g fat/kg of body weight), men had higher postprandial triglyceridemia than women on the HF diet but no such difference was observed on the LF diet. The results of this preliminary study suggest that there may be important sex differences in the mechanisms regulating the postprandial lipemia response to different diets, women being able to adapt better to the HF diet with respect to postprandial lipemia., J. Kovář, R. Poledne., and Obsahuje bibliografii
Increased and prolonged postprandial lipemia has been identified as a risk factor of cardiovascular disease. However, there is no consensus on how to test postprandial lipemia, especia lly with respect to the composition of an experimental meal. To address this question of how glucose, when added to a fat load, affects the selected parameters of postprandial lipemia, we carried out a study in 30 healthy male volunteers. Men consumed an experimental meal containing either 75 g of fat + 25 g of glucose (F+G meal) or 75 g of fat (F meal) in a control experiment. Blood was taken before the meal and at selected time points within the following 8 h. Glucose, when added to a fat load, induced an increase of glycemia and insulinemia and, surprisingly, a 20 % reduction in the response of both total and active glucagon -like peptide -1 (GLP -1) concentration. The addition of glucose did not affect the magnitude of postprandial triglyceridemia and TRL -C and TRL -TG concentrations but stimulated a faster response of chylomicrons to the test meal, evaluated by changes in apolipoprotein B -48 concentrations. The addition of glucose induced the physiological response of insulin and the lower response of GLP -1 to the test meal during the early postprandial phase, but had no effect on changes of TRL -cholesterol and TRL -TG within 8 h after the meal., K. Zemánková, J. Mrázková, J. Piťha, J. Kovář., and Obsahuje bibliografii
To understand the pathogenesis of hypercholesterolemia in Prague hereditary hypercholesterolemic (PHHC) rat, we analyzed the response of hepatic transcriptome to dietary cholesterol in PHHC and control Wistar rats. Male PHHC and Wistar rats were fed chow (C), 5 % fat (palm kernel oil) (CF) or 1 % cholesterol + 5 % fat (CHOL) diet for three weeks. Hepatic transcriptome was analyzed using Affymetrix GeneChip arrays. No differences were found in the effect of both control diets (C and CF) on lipid metabolism and gene expression of 6500 genes. Therefore, these data were pooled for further analysis. Dietary cholesterol induced accumulation of cholesterol and triacylglycerols in the liver in both strains and hypercholesterolemia in PHHC rats. However, there were no differences in response of hepatic transcriptome to CHOL diet. On the other hand, several genes were found to be differently expressed between both strains independently of the diet. Two of those genes, Apof and Aldh1a7, were studied in more detail, and their role in pathogenesis of hypercholesterolemia in PHHC rats could not been corroborated. In conclusion, the hypercholesterolemia in PHHC rats is due to physiological response of hepatic transcriptome to dietary cholesterol in different genetic background., M. Vlachová, M. Heczková, M. Jirsa, R. Poledne, J. Kovář., and Obsahuje bibliografii