Atherosclerosis pathology is the interplay between high intravascular LDL particle concentration and monocyte/macrophage presence within the sub-endothelial space of the artery. In this project, phenotypes of macrophages connected with subclinical inflammation in adipose tissue of living kidney donors were studied. Samples of subcutaneous adipose tissue of living kidney donors (n=36) were exposed to collagenase. Stromal vascular fraction (SVF) was eluted from the samples, then labeled with monoclonal antibodies (anti-CD14 and anti-calprotectin), conjugated with fluorochromes and analyzed by flow cytometry. The positive correlation between the number of total macrophages and calprotectin-positive macrophages with BMI in the subcutaneous adipose tissue of postmenopausal women was demonstrated (p<0.05; R=0.43 and p<0.01; R=0.60), whereas no positive correlation in premenopausal women and men was shown. In conclusion, we documented a significant effect of BMI increase on the presence of total macrophages in adipose tissue of postmenopausal women, in contrast to premenopausal women. This difference was much more pronounced when proinflammatory macrophages with membrane-bound calprotectin were analyzed.
- MeSH
- dospělí MeSH
- fenotyp * MeSH
- index tělesné hmotnosti * MeSH
- lidé středního věku MeSH
- lidé MeSH
- makrofágy metabolismus MeSH
- podkožní tuk metabolismus MeSH
- postmenopauza metabolismus MeSH
- tuková tkáň metabolismus MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The role of the FTO gene in obesity development is well established in populations around the world. The NYD-SP18 variant has been suggested to have a similar effect on BMI, but the role of this gene in determining BMI has not yet been verified. The objective of our study was to confirm the association between NYD-SP18 rs6971019 SNP and BMI in the Slavic population and to analyze i) the gender-specific effects of NYD-SP18 on BMI and ii) the simultaneous effect of FTO rs17817449 and NYD-SP18 on BMI. We analyzed a sample of a large adult population based on the post-MONICA study (1,191 males and 1,368 females). Individuals were analyzed three times over 9 years. NYD-SP18 rs6971019 SNP is related to BMI in males (2000/1 GG 28.3+/-3.7 kg/m(2) vs. +A 27.5+/-3.7 kg/m(2) P<0.0005; in other examinations P<0.05 and <0.005), but not in females (all P values over 0.48 in all three examinations). Further analysis revealed the significant additive effect (but not the interaction) of FTO and NYD-SP18 SNPs on BMI in males (all P<0.01). These results suggest that association between NYD-SP18 rs6971019 SNP and BMI may be restricted to males. Furthermore, variants within NYD-SP18 and FTO genes revealed a significant additive effect on BMI values in males.
- MeSH
- dospělí MeSH
- genetická variace genetika MeSH
- index tělesné hmotnosti * MeSH
- jednonukleotidový polymorfismus genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- obezita diagnóza genetika MeSH
- pohlavní dimorfismus * MeSH
- proteiny genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
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, especially 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.
- MeSH
- apolipoprotein B-48 krev MeSH
- dietní tuky aplikace a dávkování MeSH
- dospělí MeSH
- glukagonu podobný peptid 1 krev MeSH
- glukosa aplikace a dávkování MeSH
- lidé MeSH
- postprandiální období účinky léků fyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Dyslipidemia is the risk factor of cardiovascular disease, but the relationship between the plasma triglyceride (TG) levels and total/cardiovascular mortality has not yet been analyzed in Slavs. The aim of our study was to analyze the association between the fasting TG levels and all-cause/cardiovascular mortality. We have examined 3,143 males and 3,650 females, aged 58.3+/-7.1 years. 729 deaths (274 cardiovascular deaths) have been registered during up to 11.8 years of follow-up. Age-sex adjusted all-cause mortality was higher in individuals with TG values 3.01-4.00 mmol/l (HR 1.37, 95 % CI 1.02-1.83, P=0.035) and over 4.00 mmol/l (HR 1.66, 95 % CI 1.21-2.27, P=0.002) when compared with a reference group (TG 1.41-1.80 mmol/l). Elevated risk remains significant when adjusted for education, marital status and unemployment. When further adjusted for smoking, BMI and dyslipidemia interventions, HR for those in above 4.00 mmol/l group decreased (1.42, P=0.04). The results have been similar when cardiovascular mortality has been examined, however, results reached statistical significance only for the TG over 4.0 mmol/l (P=0.028). Our results confirmed that enhanced plasma levels of plasma triglycerides are dose dependently associated with increased risk of all-cause mortality, however, it seems that individuals with TG values 1.8-3.0 mmol/l are not in higher risk of death.
- MeSH
- kardiovaskulární nemoci krev mortalita MeSH
- lidé středního věku MeSH
- lidé MeSH
- mortalita trendy MeSH
- následné studie MeSH
- omezení příjmu potravy krev MeSH
- rizikové faktory MeSH
- senioři MeSH
- surveillance populace * metody MeSH
- triglyceridy krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Česká republika MeSH
The issue of plasma triglyceride levels relative to the risk of development of cardiovascular disease, as well as overall mortality, has been actively discussed for many years. Like other cardiovascular disease risk factors, final plasma TG values have environmental influences (primarily dietary habits, physical activity, and smoking), and a genetic predisposition. Rare mutations (mainly in the lipoprotein lipase and apolipoprotein C2) along with common polymorphisms (within apolipoprotein A5, glucokinase regulatory protein, apolipoprotein B, apolipo-protein E, cAMP responsive element binding protein 3-like 3, glycosylphosphatidylinositol-anchored HDL-binding protein 1) play an important role in determining plasma TG levels.
Hypertriglyceridemia is an important marker of increased levels of highly atherogenic remnant-like particles. The importance of lowering plasma levels of triglycerides (TG) has been called into question many times, but currently it is considered an integral part of residual cardiovascular risk reduction strategies. Lifestyle changes (improved diet and increased physical activity) are effective TG lowering measures. Pharmacological treatment usually starts with statins, although associated TG reductions are typically modest. Fibrates are currently the drugs of choice for hyperTG, frequently in combination with statins. Niacin and omega-3 fatty acids improve control of triglyceride levels when the above measures are inadequately effective. Some novel therapies including anti-sense oligonucleotides and inhibitors of microsomal triglyceride transfer protein have shown significant TG lowering efficacy. The current approach to the management of hypertriglyceridemia is based on lifestyle changes and, usually, drug combinations (statin and fibrate and/or omega-3 fatty acids or niacin).
- MeSH
- chování snižující riziko * MeSH
- hypertriglyceridemie krev terapie MeSH
- hypolipidemika terapeutické užití MeSH
- kyseliny mastné omega-3 terapeutické užití MeSH
- lidé MeSH
- niacin terapeutické užití MeSH
- randomizované kontrolované studie jako téma metody MeSH
- rizikové faktory MeSH
- statiny terapeutické užití MeSH
- triglyceridy krev MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Moderately elevated plasma/serum triglycerides (2-10 mmol/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 lipoproteins, 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 frequently 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 cholesterol), 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 aggressiveness of treatment.
- MeSH
- biologické markery krev MeSH
- diabetes mellitus krev diagnóza MeSH
- hypertriglyceridemie krev diagnóza MeSH
- inzulinová rezistence fyziologie MeSH
- kardiovaskulární nemoci krev diagnóza MeSH
- lidé MeSH
- omezení příjmu potravy krev MeSH
- triglyceridy krev MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- MeSH
- ateroskleróza krev diagnóza MeSH
- biologické markery krev MeSH
- hypertriglyceridemie krev diagnóza MeSH
- lidé MeSH
- mediátory zánětu krev MeSH
- triglyceridy krev MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- úvodní články MeSH
Interesting and stimulating data about the effect of the perivascular adipose tissue size on atherogenesis are based mainly on CT findings. We studied this topic by directly analyzing perivascular adipose tissue in explanted hearts from patients undergoing transplantation. Ninety-six consecutive patients were included, including 58 with atherosclerotic coronary heart disease (CHD) and 38 with dilation cardiomyopathy (DCMP). The area of perivascular fat, area of the coronary artery wall, and ratio of CD68-positive macrophages within the perivascular fat and within the vascular wall were quantified by immunohistochemistry. There was no significant difference in the perivascular adipose tissue size between the two groups. Nevertheless, there was a significantly higher number of macrophages in the coronary arterial wall of CHD patients. In addition, we found a close relationship between the ratio of macrophages in the arterial wall and adjacent perivascular adipose tissue in the CHD group, but not in the DCMP group. According to our data interaction between macrophages in the arterial wall and macrophages in surrounding adipose tissue could be more important mechanism of atherogenesis than the size of this tissue itself.
- MeSH
- ateroskleróza diagnóza metabolismus MeSH
- dospělí MeSH
- kardiomyopatie diagnóza metabolismus MeSH
- koronární cévy metabolismus patologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- nemoci koronárních tepen diagnóza metabolismus MeSH
- senioři MeSH
- transplantace srdce trendy MeSH
- tuková tkáň metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Renal transplantation is associated with a large number of risk factors that can have an influence on early renal graft function (ERGF). One of these factors could be the increasing number of obese kidney donors. The mechanisms of reduced ERGF in obese kidney donors are still poorly understood. To that end, we compared ERGF in recipients with body mass index (BMI), perivascular fat and plasma inflammation markers of live kidney donors. We hypothesized that the BMI of donors would negatively correlate with an average increase of glomerular filtration rate (GFR) and that it would also be associated with increased perivascular and plasma inflammation markers in the first seven days after transplantation. Between January 2013 and December 2014, some 58 living kidney transplantation pairs were included in the study. Donor and recipient demographic data, preoperative BMI, blood C-reactive protein (CRP) and adiponectin levels, perivascular adipose tissue (PAT) samples and recipient blood creatinine levels were analyzed. The median CRP of donors was 0.68 mg/l (max: 8.66 mg/l, min: 0.33 mg/l), the median of M1 macrophages (CD14+CD16+) in one gram of PAT was 5940 (max: 41 100, min: 248) and the median of adiponectin was 411 930 pg/ml (max: 14 217 000, min: 167 300) in plasma. We did not find any association between early renal graft function and the percentage of M1 macrophages in donor perirenal adipose tissue (p=0.83, r=0.03, n=58), adiponectin (p=0.65, r=0.06, n=58) or CRP (p=0.16, r=0.2, n=58) in plasma. The obesity level of donors, expressed as BMI, did not correlate with early renal graft function in the first seven days after transplantation. The associations between ERGF and plasma and perivascular fat inflammation markers were not significant. We confirmed a negative correlation between the BMI of recipients and an average increase of GFR in the first seven days after transplantation (p<0.02, r=-0.325, N=58). We confirmed a negative correlation of adiponectin plasma concentration to the BMI of donors.
- MeSH
- dospělí MeSH
- dyslipidemie epidemiologie metabolismus MeSH
- hodnoty glomerulární filtrace fyziologie MeSH
- hypertenze epidemiologie metabolismus MeSH
- index tělesné hmotnosti * MeSH
- lidé středního věku MeSH
- lidé MeSH
- přežívání štěpu fyziologie MeSH
- retrospektivní studie MeSH
- rizikové faktory MeSH
- transplantace ledvin škodlivé účinky trendy MeSH
- tuková tkáň metabolismus MeSH
- výsledek terapie MeSH
- žijící dárci * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH