The bone marrow has emerged as a potentially important target in cardiovascular disease as it generates all leukocytes involved in atherogenesis. In the current study, we evaluated whether a change in bone marrow functionality underlies the increased atherosclerosis susceptibility associated with high-density lipoprotein (HDL) deficiency. We found that HDL deficiency in mice due to the genetic lack of hepatocyte-derived apolipoprotein A1 (APOA1) was associated with an increase in the Lin-Sca-1+Kit+ (LSK) bone marrow stem cell population and lymphoid-primed multipotent progenitor numbers, which translated into a higher production and systemic flux of T cell subsets. In accordance with APOA1 deficiency-associated priming of stem cells to increase T lymphocyte production, atherogenic diet-fed low-density lipoprotein receptor knockout mice transplanted with bone marrow from APOA1-knockout mice displayed marked lymphocytosis as compared to wild-type bone marrow recipients. However, atherosclerotic lesion sizes and collagen contents were similar in the two groups of bone marrow recipients. In conclusion, systemic lack of APOA1 primes bone marrow stem cells for T cell lymphopoiesis. Our data provide novel evidence for a regulatory role of HDL in bone marrow functioning in normolipidemic mice.

• Klíčová slova
• Apolipoprotein, Bone marrow, High-density lipoprotein, Lymphopoiesis, Stem cells,
• MeSH
• apolipoprotein A-I * nedostatek   genetika   MeSH
• buňky kostní dřeně MeSH
• LDL-receptory MeSH
• lymfopoéza * MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• T-lymfocyty MeSH
• transplantace kostní dřeně MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• Apoa1 protein, mouse MeSH Prohlížeč
• apolipoprotein A-I * MeSH
• LDL-receptory MeSH

Proteinuria is often used as a surrogate marker in monitoring and predicting outcome in patients with chronic kidney diseases, but it is non-specific. IgAN belongs to the most common primary glomerulonephritis worldwide with serious prognosis. The main aim of this work was to assess differences in urine proteins in patients with IgA nephropathy and to identify abnormal proteins as potential biomarkers of IgA nephropathy or the renal disease. In our pilot project, we selected 20 patients and compared them with 20 healthy volunteers. Protein quantification was performed using iTRAQ (isobaric tag for relative and absolute quantitation) labeling method. The peptides were separated by the isoelectric focusing method (IEF) and nano-LC with C18 column and identified by mass spectrometry using MALDI-TOF/TOF MS. Proteins´ lists obtained from IEF-LC-MS-MS/MS analysis were combined and contained 201 proteins. It was found out that 113 proteins were common in both experiments. 30 urinary proteins were significantly up- or down-regulated in patients with IgA nephropathy. We characterized potential biomarkers such as alpha-1-antitrypsin, apolipoprotein A-I, CD44 antigen or kininogen. Potential biomarkers of IgAN should be validated in further studies.

• MeSH
• alfa-1-antitrypsin genetika   moč   MeSH
• apolipoprotein A-I genetika   moč   MeSH
• biologické markery moč   MeSH
• dospělí MeSH
• IgA nefropatie diagnóza   genetika   moč   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• pilotní projekty MeSH
• proteomika metody   MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa-1-antitrypsin MeSH
• apolipoprotein A-I MeSH
• biologické markery MeSH

Dyslipidemia (high levels of plasma triglycerides and total cholesterol/LDL-cholesterol and low HDL-cholesterol) is considered as one of the major factors in the development of atherosclerosis and subsequent myocardial infarction. The final value of lipid parameters results from joint action of genetic predispositions and lifestyle factors (primarily smoking status, physical activity and in lower extent also diet). It is estimated that genetic factors are responsible for 40-80 % of the variability of plasma lipid values. Currently are as predictors DL analyzed mainly single nucleotide polymorphisms (SNPs). A fundamental shift in knowledge of genetic determination DL bring genome-wide association studies (GWAs). These revealed several dozen major polymorphisms in a DNA sequence related to lipid levels. Rather surprisingly, these variants are usually not substitutions of the amino acids, or causing a premature stop codon, but substitutions outside the genes. GWAS also found a number of variants within the genes whose function in lipid metabolism was completely unknown (e.g. gene for sortilin). Polymorphisms in genes for APOE, SORT1, LDLR (affect levels of total cholesterol and LDL-cholesterol), CETP, APOA1, ABCA-1, GALNT-2 (influence HDL-cholesterol) and finally in genes for APOA5, LPL or TRIB1 (affect the levels of triglycerides) but explains max. 30 % of the variability of plasma lipids. It is supposed, that rare polymorphisms/mutations and genetic factors unrelated directly to alterations in the DNA sequence (DNA methylation, histone modifications, regulatory RNA molecules) are responsible for the remaining proportion of DL determination.Key words: gene - cholesterol - interaction - mutation - polymorphism - triglycerides.

• MeSH
• ABCA1 protein genetika   MeSH
• adaptorové proteiny vezikulární transportní genetika   MeSH
• apolipoprotein A-I genetika   MeSH
• apolipoprotein A-V genetika   MeSH
• apolipoproteiny E MeSH
• ateroskleróza MeSH
• celogenomová asociační studie MeSH
• dyslipidemie krev   genetika   MeSH
• epigeneze genetická genetika   MeSH
• genetická predispozice k nemoci MeSH
• HDL-cholesterol krev   MeSH
• histonový kód genetika   MeSH
• intracelulární signální peptidy a proteiny genetika   MeSH
• jednonukleotidový polymorfismus MeSH
• LDL-cholesterol krev   MeSH
• LDL-receptory genetika   MeSH
• lidé MeSH
• lipidy krev   MeSH
• lipoproteinlipasa genetika   MeSH
• metabolismus lipidů genetika   MeSH
• metylace DNA genetika   MeSH
• N-acetylgalaktosaminyltransferasy genetika   MeSH
• polypeptid-N-acetylgalaktosaminyltransferasa MeSH
• protein-serin-threoninkinasy antagonisté a inhibitory   genetika   MeSH
• transportní proteiny pro estery cholesterolu genetika   MeSH
• triglyceridy krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ABCA1 protein, human MeSH Prohlížeč
• ABCA1 protein MeSH
• adaptorové proteiny vezikulární transportní MeSH
• APOA1 protein, human MeSH Prohlížeč
• APOA5 protein, human MeSH Prohlížeč
• apolipoprotein A-I MeSH
• apolipoprotein A-V MeSH
• apolipoproteiny E MeSH
• CETP protein, human MeSH Prohlížeč
• HDL-cholesterol MeSH
• intracelulární signální peptidy a proteiny MeSH
• LDL-cholesterol MeSH
• LDL-receptory MeSH
• LDLR protein, human MeSH Prohlížeč
• lipidy MeSH
• lipoproteinlipasa MeSH
• LPL protein, human MeSH Prohlížeč
• N-acetylgalaktosaminyltransferasy MeSH
• protein-serin-threoninkinasy MeSH
• sortilin MeSH Prohlížeč
• transportní proteiny pro estery cholesterolu MeSH
• TRIB1 protein, human MeSH Prohlížeč
• triglyceridy MeSH

BACKGROUND: The relationship between dietary composition and plasma lipids is to some extent genetically determined. It has been found that variants of some genes (e.g., apolipoprotein E and cholesterol 7-alpha hydroxylase) play an important role in changes in plasma lipid levels in response to dietary intervention. We analyzed the effect of variation in the apolipoprotein (APO) APOA1/C3/A4/A5 gene cluster on decreases in plasma cholesterol levels over an 8-year follow-up study. METHODS: Men (n=133) from the Czech population, for which dietary composition has markedly changed (red meat 80-->68 kg/person/year, animal fat 16-->9 kg/person/year, fruits and vegetables 133-->150 kg/person/year) were recruited. APOA1 (G-75>A and C83>T), APOC3 (C-482>T and C3238>G), APOA4 (Thr347>Ser and Gln360His) and APOA5 (T-1131>C, Ser19>Trp and Val153>Met) variants were analyzed by PCR and restriction analysis. Lipid levels were analyzed in 1988 and 1996. Dietary information was obtained from the Institute of Agricultural Economy. RESULTS: In APOA5 Ser19Ser homozygotes (n=105), plasma cholesterol was relatively stable over the years (6.1+/-1.3 and 5.6+/-1.0 mmol/L in 1988 and 1996), but the decrease was much higher in Trp19 carriers (n=27; 6.5+/-1.6 vs. 5.1+/-1.1 mmol/L). This difference in change is significant at p<0.005. Similarly, a better response to dietary changes was detected in carriers of the common APOA4 haplotypes Thr-347Thr/Gln360Gln and Thr347Ser/Gln360Gln (n=102; 6.3+/-1.3 and 5.5+/-1.1 mmol/L in 1988 and 1996, p<0.001). Total cholesterol was relatively stable over time in carriers (n=18) of at least one His360 allele and/or two Ser347 alleles (5.7+/-1.1 and 5.5+/-0.9 mmol/L in 1988 and 1996, n.s.). Other variants analyzed did not influence the change in lipid measurements over time. CONCLUSIONS: APOA4 and APOA5 variants may play an important role in the individual sensitivity of lipid parameters to dietary composition in men.

• MeSH
• apolipoprotein A-I genetika   MeSH
• apolipoprotein A-V MeSH
• apolipoprotein C-III genetika   MeSH
• apolipoproteiny A genetika   MeSH
• cholesterol krev   MeSH
• dieta * MeSH
• DNA genetika   izolace a purifikace   MeSH
• dospělí MeSH
• genetická variace MeSH
• homozygot MeSH
• lidé středního věku MeSH
• lidé MeSH
• multigenová rodina MeSH
• následné studie MeSH
• polymorfismus genetický * MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• APOA5 protein, human MeSH Prohlížeč
• apolipoprotein A-I MeSH
• apolipoprotein A-IV MeSH Prohlížeč
• apolipoprotein A-V MeSH
• apolipoprotein C-III MeSH
• apolipoproteiny A MeSH
• cholesterol MeSH
• DNA MeSH

The activity of lipoprotein lipase (LPL) is increased after alcohol consumption and can contribute to an increased level of HDL-cholesterol, which is considered to play a key role in the ethanol-mediated protective effect against cardiovascular disease. The increase in HDL-cholesterol concentration can be also due to an ethanol-enhanced synthesis and secretion of apolipoprotein A-I (apo A-I) from hepatocytes. Therefore, the hypothesis that ethanol consumption affects the LPL and apo A-I gene (LPL and APOA1, respectively) expression was tested in male C57BL/6 mice drinking 5 % ethanol or water and fed a standard chow or high-fat (HF) diet for 4 weeks. The LPL expression was determined in the heart, epididymal and dorsolumbal adipose tissues, the APOA1 expression in the liver. Alcohol consumption did not affect lipid and lipoprotein concentrations in the serum. The LPL expression was increased in the heart of mice given ethanol and HF diet compared to mice on chow and ethanol (p<0.001) and was also increased in epididymal fat in mice given ethanol and HF diet compared to mice on water and HF diet (p<0.05). Neither LPL expression in dorsolumbal fat nor APOA1 expression in the liver were affected by ethanol consumption. Our data suggest that ethanol consumption upregulates LPL expression in a tissue- and diet-dependent manner.

• MeSH
• apolipoprotein A-I genetika   metabolismus   MeSH
• časové faktory MeSH
• dietní tuky aplikace a dávkování   MeSH
• ethanol aplikace a dávkování   MeSH
• látky tlumící činnost CNS aplikace a dávkování   MeSH
• lipidy krev   MeSH
• lipoproteinlipasa genetika   metabolismus   MeSH
• messenger RNA metabolismus   MeSH
• myokard enzymologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• pití alkoholu metabolismus   MeSH
• regulace genové exprese enzymů účinky léků   MeSH
• tuková tkáň účinky léků   enzymologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• apolipoprotein A-I MeSH
• dietní tuky MeSH
• ethanol MeSH
• látky tlumící činnost CNS MeSH
• lipidy MeSH
• lipoproteinlipasa MeSH
• messenger RNA MeSH

OBJECTIVES: We investigated associations between single nucleotide polymorphisms (SNPs) in the hepatic lipase promoter, levels of high-density lipoprotein (HDL), and risk of ischemic heart disease (IHD). Our primary hypothesis was that these SNPs associate with IHD after adjustment for HDL levels. BACKGROUND: Hepatic lipase influences HDL metabolism, and may thus affect reverse cholesterol transport and consequently risk of IHD. METHODS: We genotyped 9,121 white subjects aged 20 to 93 years from the Copenhagen City Heart Study, 456 of whom had incident IHD, as well as 921 Danish patients with IHD for the -216, -480, and -729 SNPs in the hepatic lipase promoter. RESULTS: Frequencies of wild-type, triple heterozygotes, and triple mutation homozygotes in the general population were 61%, 33%, and 5%, respectively. Compared with wild-type, HDL cholesterol levels were 4% (0.06 mmol/l) and 10% (0.15 mmol/l) higher in heterozygotes and mutation homozygotes; the equivalent values for apolipoprotein A1 were 3% and 7% higher. In prospective and case-control studies, mutation homozygotes versus wild-type had relative risk (RR) and odds ratio (OR) for IHD of 1.5 (95% confidence interval [CI]: 1.0 to 2.2) and 1.4 (CI: 1.1 to 1.9) when adjusted for age, gender, and HDL cholesterol. In individuals with the epsilon43 apolipoprotein E genotype, RR and OR for IHD in mutation homozygotes versus wild-type was 2.9 (CI: 1.5 to 5.6) and 2.0 (CI: 1.2 to 3.2). CONCLUSIONS: Hepatic lipase promoter SNPs are associated with increased HDL cholesterol and, paradoxically, an increased risk of IHD after adjustment for HDL cholesterol, and particularly in individuals with apolipoprotein E epsilon43 genotype. Implications are that increased HDL levels may in certain situations be not protective, but rather associated with increased IHD risk.

• MeSH
• apolipoprotein A-I genetika   metabolismus   MeSH
• apolipoproteiny E genetika   metabolismus   MeSH
• dospělí MeSH
• frekvence genu genetika   MeSH
• genetické markery genetika   MeSH
• genotyp MeSH
• HDL-cholesterol genetika   metabolismus   MeSH
• ischemická choroba srdeční epidemiologie   genetika   metabolismus   MeSH
• játra enzymologie   metabolismus   MeSH
• LDL-cholesterol genetika   metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipasa genetika   metabolismus   MeSH
• mutace genetika   MeSH
• prediktivní hodnota testů MeSH
• promotorové oblasti (genetika) genetika   MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• rizikové faktory MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• statistika jako téma MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Názvy látek
• apolipoprotein A-I MeSH
• apolipoproteiny E MeSH
• genetické markery MeSH
• HDL-cholesterol MeSH
• LDL-cholesterol MeSH
• lipasa MeSH

Genetic and environmental factors regulate lipid metabolism and phenotypic expression of CAD. In this study we assessed the effects of apoE gene polymorphism and apoA1 gene promoter polymorphism on lipid metabolism and risk for CAD. In a case-control study, 166 patients with CAD were compared with 130 healthy subjects. The apoE allele frequencies of patients vs. control group were 6.3% vs. 7.7% for e2, 84.3% vs. 84.6% for e3, and 9.4% vs. 7.7% for e4. Individuals with e3e4 and e4e4 genotypes had higher total (P = 0.023) and LDL cholesterol levels (P = 0.04) than individuals with other genotypes. There were no differences in lipid parameters between the subjects with the apoA1-GG genotype and subjects with AG or AA genotypes. However, univariate analysis revealed no association between risk genotypes (e3e4 and e4e4 genotypes) of apoE and CAD risk (OR = 1.1; 95% CI = 0.6-2.1, P = 0.8) as well as no association between the GG genotype and CAD risk (OR 0.7; 95% CI = 0.5-1.2, P = 0.19). No evidence for a synergistic interaction between e3e4 plus e4e4 genotypes and apoA1-GG genotype on CAD risk was found (OR = 1.3, 95% CI = 0.6-2.9; P = 0.5). One individual with familial defective apolipoprotein B-100 (Arg3500Gln) was found in each group. In conclusion, the apoE gene polymorphism affected the total and LDL cholesterol levels, whereas neither the apoE gene polymorphism nor the apoA-1 gene promoter polymorphism were shown to be independent risk factors for CAD in Slovenia.

• MeSH
• alely MeSH
• apolipoprotein A-I genetika   MeSH
• apolipoproteiny E genetika   MeSH
• cholesterol krev   MeSH
• fenotyp MeSH
• frekvence genu MeSH
• genotyp MeSH
• HDL-cholesterol krev   MeSH
• koronární nemoc krev   genetika   patofyziologie   MeSH
• LDL-cholesterol krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipidy krev   MeSH
• polymorfismus genetický * MeSH
• promotorové oblasti (genetika) * MeSH
• referenční hodnoty MeSH
• rizikové faktory MeSH
• triglyceridy krev   MeSH
• věk při počátku nemoci MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• apolipoprotein A-I MeSH
• apolipoproteiny E MeSH
• cholesterol MeSH
• HDL-cholesterol MeSH
• LDL-cholesterol MeSH
• lipidy MeSH
• triglyceridy MeSH