There is increasing evidence that dietary saturated fatty acids (SAFA) have not only an indirect atherogenic effect due to increasing LDL-cholesterol concentration but also a direct effect by activating the inflammation process. This review summarizes several recent publications in this field. The effect of SAFA on the inflammation process mediated by Toll-like receptor 4/NF-κB pathway has been well documented in various in vitro culture studies of macrophages and adipocytes or in their co-culture. In contrast to these in vitro data, in vivo epidemiological studies or clinical experiments in men are less consistent. Well controlled cross-over studies in volunteers might enlighten the differences between saturated and unsaturated fatty acids dietary intake and proatherogenic inflammation effects., R. Poledne., and Obsahuje seznam literatury
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
Apolipoproteins E and CI are the predominant components of triglyceride-rich lipoproteins. The genes are located in one gene cluster and both are polymorphic. Three allelic (ε2, ε3 and ε4) polymorphisms of the APOE gene influence plasma cholesterol levels. The distribution of these alleles differ between ethnic groups. PCR genotyping was used to determine the APOE and APOCI allele incidence in a representative group of 653 probands (302 men and 351 women) of Czech origin. The observed relative frequencies for the ε2, ε3 and ε4 alleles were 7.1 %, 82.0 % and 10.9 %, respectively, and are similar to other middle European populations. APO ε4 carriers have the highest and APO ε2 carriers the lowest levels of plasma total cholesterol (p<0.0001) and LDL cholesterol (p<0.0001). The frequency of the insertion (I) allele (HpaI restriction site present) of the APOCI polymorphism was 18.5 %. APOCI I/I homozygotes have the highest level of triglycerides (p<0.003). An almost complete linkage disequilibrium of the insertion allele of APOCI with the APOE alleles ε2 and ε4 has been detected and suggests that the deletion in the APOCI gene probably follows the deriving of all three APOE alleles on the APO ε3 allele background., J. A. Hubáček, J. Piťha, V. Adámková, Z. Škodová, V. Lánská, R. Poledne., and Obsahuje bibliografii
Replacing SAFAs (saturated fatty acids) for vegetable PUFAs (polyunsaturated fatty acids) has a well documented positive effect on the lipoprotein pattern while the direct effect of dietary fatty acids composition on systemic inflammation remains to be proven. In well controlled randomised cross-over study with 15 overweight/obese postmenopausal women, the effect of dietary switch on systemic inflammation was investigated. A two 3 weeks dietary period either with predominant animal fat (SAFA, 29 caloric % SAFA) or vegetable fat (PUFA 25 % caloric % PUFA) were interrupted by wash-out period. The expected increasing effect on SAFA diet to LDL-C (low density cholesterol) and opposite effect of PUFA diet was documented following changes in fatty acid spectrum in VLDL (very low density cholesterol) particles. The switch from SAFA diet to PUFA diet produced a significant change of CRP (C-reactive protein) concentration (p<0.01) whereas similar trend of IL-18 did not reach statistical significance. In this study, previous in vitro results of different SAFA and PUFA proinflammatory effects with well documented molecular mechanisms were first proven in a clinical study. It could be stated that the substantial change of dietary fatty acid composition might influence proinflammatory effect in addition to traditional cardiovascular risk factors., I. Králová Lesná, ... [et al.]., and Obsahuje seznam literatury
The first experimental model of atherosclerosis (in rabbits) is more than hundred years old. Several animal species have bee n used to produce hyperlipoproteine mia and possible atherosclerosis. The gene manipulation produced the most used models recently. This review acknowledges the extensive study of atherosclerotic changes in experimental models of hyperlipoprotein emia and at herosclerosis to come to light thus far and the purpose here is not only to summariz e the published data but also to try to add some details of our experience in using these models. In addition to rabbit (the old but also improved model by reno-vascular hy pertension) dog, birds, pig, hamster, mice, rat and non-human primate’s animal models are described. The gene manipulation produced the most used models two decades ago. Germline genetically engineered (without apoE or LDL receptor genes) animals have beco me the most used models producing atherosclerotic changes in the aorta. Recent new models also producing atherosclerotic changes but without germline genetic manipulation are also described., R. Poledne, L. Jurčíková-Novotná., and Obsahuje bibliografii
Atherosclerosis is a degenerative inflammatory disease of the vascular wall, which is characterized by the formation of atherosclerotic plaques that contain lipids, activated smooth muscle cells, immune cells, foam cells, a necrotic core and calcified sites. In atherosclerosis pathology, monocytes and macrophages play the most important role by accumulating redundant LDL particles in their oxidized form and producing proinflammatory cytokines. Atherosclerotic plaque macrophages reveal distinct phenotypes that are distinguished into M1 (proinflammatory) and M2 (anti-inflammatory) macrophages. Numerous environmental signals (cytokines, microbial cell molecules) that are received by macrophages drive their polarization, but it must be determined whether this classification reflects different macrophage subtypes or plasticity and phenotypic tissue changes, but the balance between subsets is crucial. M1 macrophages are dominant in symptomatic atherosclerotic plaques, while M2 macrophages are more frequent in asymptomatic plaques. Nevertheless, a positive correlation of both M1 and M2 macrophages with atherosclerotic lesion severity was also observed., A. Králová, I. Králová lesná, R. Poledne., and Obsahuje bibliografii
A low birth weight is a new risk factor for the development of premature atherosclerosis. The effect of intrauterine undernutrition on hypercholesterolemia in later life was studied in an experimental model using the Prague Hereditary Hypercholesterolemic (PHHC) rat. Compared to animals in the control group (Wistar rats), animals with an increased sensitivity to high-cholesterol diet (PHHC rats) display hypercholesterolemia. Only in PHHC animals, individuals undernourished in their intrauterine life (hypotrophic group, HG) had a significantly higher total cholesterol, compared with individuals without food restriction in pregnancy (eutrophic group, EG). Restricted food intake in pregnancy led to smaller nests and a decreased number of pups in each litter. We found no significant diferences in birth weight between HG and EG. In spite of similar birth weights in PHHC and Wistar rats, intrauterine undernutrition caused an increase in cholesterolemia in the HG group of the PHHC rats. The effect of intrauterine undernutrition on the development of hypercholesterolemia will most likely play a role in individuals with geneticaly determined increased susceptibility to a high-cholesterol diet. The use of this model of intrauterine undernutrition for the study of hypercholesterolemia has proved to be feasible., P. Szitányi, J. Hanzlová, R. Poledne., and Obsahuje bibliografii
It is believed that atherogenesis is a multifactorial process, which could already start in utero. Development of atherosclerosis progresses over decades and leads to the cardiovascular morbidity and mortality in adulthood. At present, we have no exact explanation for all the risk factors acting in the pathogenesis of atherosclerosis. This review should provide an overview about the possible role of intrauterine undernutrition in the development of risk factors for cardiovascular disease. Intrauterine undernutrition leads to changes in fetal growth and metabolism and programs later development of some of these risk factors. A number of experimental and human studies indicates that hypertension as well as impaired cholesterol and glucose metabolism are affected by intrauterine growth. Intrauterine undernutrition plays an important role and acts synergistically with numerous genetic and environmental factors in the development of atherosclerosis. There is evidence that undernutrition of the fetus has permanent effects on the health status of human individuals., P. Szitányi, J. Janda, R. Poledne., and Obsahuje bibliografii
It is well known that the consumption of moderate doses of alcohol leads to the increase of HDL-cholesterol (HDL-C). Atheroprotectivity of HDL particles is based primarily on their role in reverse cholesterol transport (RCT). In the study with a crossover design 13 male volunteers were studied in two different regimens: i) drinking of 36 g alcohol daily and ii) drinking only non-alcoholic beverages, to test whether alcohol-induced increase of HDL cholesterol can affect cholesterol efflux (CHE) from cell culture of labeled human macrophages. Alcohol consumption induced significant (p<0.05) increases of HDL cholesterol from 1.25±0.32 to 1.34±0.38 mmol/l and Apo A1 from 1.34±0.16 to 1.44±0.19 g/l. These changes were combined with a slight increase of cholesterol efflux from 13.8±2.15 to 14.9±1.85 % (p=0.059). There were significant correlations between individual changes of HDL-C and Apo A1 concentrations and individual changes of CHE (0.51 and 0.60, respectively). In conclusion, moderate alcohol consumption changes the capacity of plasma to induce CHE only at a border line significance., I. Králová Lesná ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
We have determined the genotypes of two common polymorphisms in the lipoprotein lipase (S447X) and hepatic lipase (-480C/T) genes in a cohort of 285 representative selected Czech probands (131 male and 154 female), examined in 1988 and reinvestigated in 1996. The genotype distributions of both polymorphisms were in Hardy-Weinberg equilibrium and did not differ between male and female subjects. The rare allele frequency of the lipoprotein lipase polymorphism did not differ significantly from the other European populations. Compared to the German populations, the frequency of the hepatic lipase -480T allele was significantly higher in the Czech group (20 % vs. 36 %, p<0.0001). There were no significant associations between the lipoprotein lipase gene variants and lipid parameters measured either in 1988, or in 1996 or with changes of lipid parameters over the 8-year period. The carriers of the T-480 allele of the hepatic lipase polymorphism were found to have higher HDL cholesterol levels (p=0.02). However, this difference was confined to female subjects only. The male carriers of the -480T allele had higher concentrations of total cholesterol (p=0.03) as compared to CC-480 subjects. Both associations were observed in 1996 only. In the Slavic Czech population, a common polymorphism in the hepatic lipase gene (-480C/T), but not in the lipoprotein lipase gene (S447X), is a significant determinant of plasma HDL cholesterol in females and plasma total cholesterol in males and indicates the importance of gender-associated effects in the genetic determinations of plasma lipids., J.A. Hubáček, D.M. Waterworth, J. Piťha, S.E. Humphries, P.J. Talmud, R. Poledne., and Obsahuje bibliografii