• Klíčová slova
• familiární chylomikronemie, Inklisiran,
• MeSH
• apolipoprotein A-I biosyntéza   farmakologie   MeSH
• apolipoprotein C-III antagonisté a inhibitory   MeSH
• deriváty kyseliny fibrové farmakologie   MeSH
• humanizované monoklonální protilátky farmakologie   terapeutické užití   MeSH
• hypercholesterolemie * farmakoterapie   MeSH
• hyperlipoproteinemie typ II komplikace   parazitologie   MeSH
• hypolipidemika * farmakologie   terapeutické užití   MeSH
• klinické zkoušky, fáze III jako téma MeSH
• PCSK9 inhibitory farmakologie   terapeutické užití   MeSH
• randomizované kontrolované studie jako téma MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND AND AIM: Since hepatocytes produce majority of serum proteins, patients with cirrhosis display substantial alterations in the serum proteome. The aim of the current study was to characterize these changes and to study the prognostic utility of hepatocellular proteins available in routine clinical testing. METHODS: Sera from 29 healthy controls and 43 patients with cirrhosis were subjected to untargeted proteomic analysis. Unsupervised hierarchical clustering was performed with Perseus software and R. Ingenuity pathway analysis (IPA) suggested upstream regulators that were validated in liver tissues. The behavior and prognostic usefulness of selected biomarkers was investigated in 61 controls and 285 subjects with decompensated cirrhosis. RESULTS: Proteomics uncovered 65 and 16 hepatocellular serum proteins that are significantly downregulated or upregulated in patients with cirrhosis vs. controls. Hierarchical clustering revealed two main clusters and six sub-clusters. IPA identified HNF4α and IL-6 as the two major upstream regulators that were confirmed by hepatic gene expression analyses. Among pseudocholinesterase, transferrin, transthyretin, albumin, and apolipoprotein AI (Apo-AI), Apo-AI was the best predictor of 90-days transplant-free survival (AUROC 0.678; p = 0.0001) and remained an independent predictor in multivariable Cox independently of the presence of acute-on-chronic liver failure. CONCLUSION: Our study reveals cirrhosis-associated changes in hepatocellular serum proteins and underlying transcription factors. Serum apolipoprotein AI may constitute a useful prognostic adjunct in patients with decompensated cirrhosis.

• MeSH
• apolipoprotein A-I MeSH
• biologické markery MeSH
• fibróza MeSH
• hepatocelulární karcinom * MeSH
• jaterní cirhóza MeSH
• krevní proteiny MeSH
• lidé MeSH
• nádory jater * MeSH
• prognóza MeSH
• proteomika MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

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.

• MeSH
• apolipoprotein A-I * nedostatek   genetika   MeSH
• buňky kostní dřeně MeSH
• lymfopoéza * MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• receptory LDL 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

BACKGROUND: The role of cholesterol homeostasis in neuroaxonal injury in multiple sclerosis is not known. OBJECTIVE: The objective of the study is to investigate the associations of cerebrospinal fluid (CSF) and serum neurofilament light chain levels (CSF-NfL and sNfL, respectively), which are biomarkers of neuroaxonal injury, with cholesterol biomarkers at the clinical onset of multiple sclerosis. METHODS: sNfL, serum cholesterol profile (total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), serum apolipoprotein (Apo) levels (ApoA-I, ApoA-II, ApoB, and ApoE), and albumin quotient were obtained for 133 patients (63% female, age: 29.9 ± 8.0 years) during the first demyelinating event. CSF-NfL was available for 103 (77%) patients. RESULTS: CSF-NfL and sNfL were negatively associated with serum ApoA-II (P = .005, P < .001) and positively associated with albumin quotient (P < .001, P < .0001). In addition, higher CSF-NfL was associated with lower serum ApoA-I (P = .009) levels and higher sNfL was associated with lower high-density lipoprotein cholesterol (P = .010). In stepwise regression, age (P = .045), serum ApoA-II (P = .022), and albumin quotient (P < .001) were associated with CSF-NfL; albumin quotient (P = .002) and ApoA-II (P = .001) were associated with sNfL. Path analysis identified parallel pathways from ApoA-II (P = .009) and albumin quotient (P < .001) to the sNfL outcome that were mediated by CSF-NfL (P < .001). The associations of CSF-NfL with ApoA-I (P = .014) and ApoA-II (P = .015) and sNfL with ApoA-II (P < .001) remained significant after adjusting for number of contrast-enhancing lesions and T2 lesion volume. CONCLUSION: Lower serum ApoA-II and ApoA-I levels are associated with greater neuroaxonal injury as measured by CSF-NfL.

• MeSH
• apolipoprotein A-I krev   MeSH
• apolipoprotein A-II krev   MeSH
• dospělí MeSH
• lidé MeSH
• longitudinální studie MeSH
• neurofilamentové proteiny mozkomíšní mok   MeSH
• neuroprotektivní látky krev   mozkomíšní mok   MeSH
• prognóza MeSH
• prospektivní studie MeSH
• roztroušená skleróza krev   mozkomíšní mok   patologie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

V rámci projektu MedPed (Make Early Diagnosis to Prevent Early Deaths) byla v naší lipidové ambulanci vyšetřena pacientka s familiární hypercholesterolemií. Při dalším vyšetření rodiny byly u její sestry zjištěny naopak velmi nízké hodnoty celkového i LDL-cholesterolu a velmi nízká (prakticky neměřitelná) koncentrace HDL-cholesterolu. Diferenciálně diagnosticky bylo vysloveno podezření na vzácnou formu familiární hypoalfalipoproteinemie, tzv. Tangierskou nemoc. Toto podezření pak bylo potvrzeno molekulárně genetickým vyšetřením. Tangierská nemoc je vrozené onemocnění lipidového metabolismu charakterizované extrémně nízkou koncentrací HDL-cholesterolu, apolipoproteinu A -I a akumulací esterů cholesterolu v makrofázích. První případ Tangierské nemoci byl popsán v roce 1961 na ostrově Tangier. V naší práci popisujeme prvního pacienta s homozygotní formou Tangierské nemoci v České republice.

Within the project MedPed (Make Early Diagnosis to Prevent Deaths) we have examined patient with familial hypercholesterolemia in our lipid ambulance. During the following investigation of the patient‘s family we found out that her sister has on the contrary very low levels of total and LDL-cholesterol. Concentration of HDL-cholesterol was extreamly low (almost immeasurable). Differential diagnosis uttered a suspicion of rare form of familial hypoalfalipoproteinemia so-called Tangier disease. This suspicion was then confirmed by molecular genetic examination. Tangier disease is a rare lipoprotein metabolism disorder characterized biochemically by almost complete absence of plasmatic HDL- cholesterol, extremely low level of apolipoprotein A-I and accumulation of cholesterol esters in macrophages. The first case was recorded on the Tangier island in 1961. In our research we describe the first case of a patient with homozygous form of Tangier disease in the history of the Czech Republic.

• Klíčová slova
• nízký LDL-cholesterol,
• MeSH
• apolipoprotein A-I MeSH
• fenotyp MeSH
• genetické testování MeSH
• HDL-cholesterol MeSH
• hyperlipoproteinemie typ II dietoterapie   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• rodina MeSH
• tangierská nemoc * diagnóza   genetika   MeSH
• výsledek terapie MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• kazuistiky MeSH

BACKGROUND: Diseases caused by atherosclerosis play the most important role in mortality and morbidity worldwide. Serum adipocyte fatty acid binding protein (A-FABP) seems to be a new promising marker to determine the risk of atherosclerosis. OBJECTIVE: The aim of this study was to evaluate relationships between serum A-FABP levels in studied individuals and to assess the possibility of modeling the intima media thickness of the common carotid artery (C-IMT) using A-FABP levels and other observed characteristics. METHODS: Seventy two Caucasian individuals were enrolled and divided into 3 groups: dyslipidemic patients with or without metabolic syndrome (MetS+, n=17; MetS-, n= 34) and controls (n=21). RESULTS: There was confirmed the well-established risk profile of individuals with MetS (unfavorable lipid and lipoprotein profile, as well as increased parameters of insulin resistence and C-IMT). A-FABP concentrations in this group were significantly higher in comparison with both MetS- and controls. CONCLUSION: Using multiple linear regression models of C-IMT values for all individual data, healthy controls and dyslipidemic patients without metabolic syndrome (MetS-) A-FABP levels were not revealed as an important predictor of C-IMT in our model. In contrast, age, gender, waist circumference, nonHDL cholesterol levels and ApoB/ApoA1 ratio were important repressors of C- IMT in study individuals. This finding may be attributed to the overwhelming effect of other more robust risk factors for atherosclerosis in these individuals.

• MeSH
• apolipoprotein A-I krev   MeSH
• apolipoprotein B-100 krev   MeSH
• arteria carotis communis diagnostické zobrazování   MeSH
• ateroskleróza krev   diagnostické zobrazování   MeSH
• dospělí MeSH
• dyslipidemie krev   diagnostické zobrazování   MeSH
• intimomediální šíře tepenné stěny MeSH
• inzulinová rezistence MeSH
• lidé středního věku MeSH
• lidé MeSH
• metabolický syndrom krev   diagnostické zobrazování   MeSH
• nemoci arterie carotis krev   diagnostické zobrazování   MeSH
• proteiny vázající mastné kyseliny krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Ze starých epidemiologických populačních studií bylo známo, že koncentrace HDL-cholesterolu (HDL-C) byla v negativní asociaci s rizikem koronárních příhod. V posledních 10 letech se objevují studie, které objevují závislost tvaru křivky U, tj. nižší a vyšší hladiny HDL-C než optimální jsou v asociaci s exponenciálně se zvyšujícím rizikem. Asociace vysokých hladin HDL-C s vysokým kardiovaskulárním rizikem není zcela jasná. Předpokládá se změna funkce velkých HDL-částic bohatých na estery cholesterolu, které se stávají donorem cholesterolu pro arterie.

It is very well known from the old epidemiological population studies, that HDL-cholesterol (HDL-C) was in a negative association with coronary events risk. New studies have occurred during the last 10 years that the mentioned association has in fact the U-shaped curve, i.e. lower and higher levels of HDL-C then the optimal one are in an exponential increasing risk. The association of high HDL-C levels with cardiovascular risk is not explained clearly. There might be a hypothesis concerning a change of function of large HDL particles riched of cholesterol esters, which become to be cholesterol donors for the arteries.

• Klíčová slova
• kardiovaskulární riziko,
• MeSH
• apolipoprotein A-I krev   MeSH
• biologické markery MeSH
• dospělí MeSH
• HDL-cholesterol * fyziologie   krev   škodlivé účinky   MeSH
• kardiovaskulární nemoci * klasifikace   mortalita   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoproteiny HDL MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• přehledy 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

• MeSH
• apolipoprotein A-I krev   MeSH
• infarkt myokardu krev   MeSH
• lidé MeSH
• proteom * MeSH
• sacharidy chemie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• práce podpořená grantem MeSH

OBJECTIVES: The mean platelet volume (MPV) and red cell distribution width (RDW) have recently arisen interest because of their association with an increased cardiovascular risk. The aim of our study was, therefore, to determine whether an association exists between MPV, RDW and lipoprotein sub-fractions, and to show the impact of statin therapy on these new possible biomarkers of atherosclerotic risk. DESIGN AND METHODS: A cohort of 40 patients with hypercholesterolaemia (29 females, mean age 62.9±9 years), without previous hypolipidaemic treatment were enrolled. The patients were treated with atorvastatin 40 mg/day for 12 weeks. Total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density cholesterol (HDL-C), triglycerides (TG), LDL-C sub-fractions [large LDL-C 1-2 and small dense (sd)-LDL-C 3-7], apolipoproteins (apoA1, apoB), apoB/apoA1 ratio, atherogenic index of plasma (AIP), haematological parameters (including MPV, RDW) and safety parameters (renal, hepatic) were measured before and after 12 weeks of atorvastatin treatment. RESULTS: At baseline, a strong correlation between HDL-C, TG, sd-LDL-C, apoB, apoB/apoA1, and AIP with MPV (r=-0.55, p<0.001; r=0.57, p<0.001; r=0.73, p<0.001; r=0.41, p<0.05; r=0.52, p<0.001; r=0.61, p<0.001, respectively) and RDW (r=-0.49, p<0.001; r=0.62, p<0.001; r=0.67, p<0.001; r=0.41, p<0.05; r=0.43, p<0.05; r=0.65, p<0.001, respectively) was found. After 12 weeks of treatment with atorvastatin, MPV and RDW values underwent significant modification only in those patients displaying the strongest lipid-lowering effect. CONCLUSIONS: Values of MPV and RDW seem to reflect a pro-atherogenic lipoprotein profile mainly represented by the presence of sd-LDL-C.

• MeSH
• anticholesteremika terapeutické užití   MeSH
• apolipoprotein A-I krev   MeSH
• apolipoprotein B-100 krev   MeSH
• ateroskleróza krev   MeSH
• atorvastatin terapeutické užití   MeSH
• dyslipidemie krev   farmakoterapie   MeSH
• erytrocytární znaky účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• pilotní projekty MeSH
• senioři MeSH
• střední objem trombocytu * MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH