Plasminogen activator inhibitor-1 (PAI-1) impedes brain plasmin synthesis. Reduced plasmin activity facilitates cumulation of amyloid beta (Aβ) in Alzheimer's disease (AD). Since plasmin also regulates the synaptic activity, it is possible that altered PAI-1 is present in other neurodegenerative disorders. We investigated whether PAI-1 and its counter-regulatory tissue plasminogen activator (tPA) are altered in serum of patients with dementia due to frontotemporal lobar degeneration (FTLD). Thirty five FTLD patients (21 in mild cognitive impairment stage (MCI) and 14 in dementia stage) and 10 cognitively healthy controls were recruited. Serum tPA and PAI-1 protein levels were measured by anova. Correlation between biochemical and demographic data were explored by measuring Pearson correlation coefficient. Serum PAI-1 levels were elevated in the FTLD dementia group as compared to FTLD MCI and controls. tPA serum levels and PAI-1/tPA ratio did not significantly differ among groups. There was a negative correlation between PAI-1 serum levels and disease severity measured by MMSE score. No correlations of tPA serum levels and PAI-1/tPA ratio with MMSE were found. Increased PAI-1 serum levels may serve as a marker of dementia in FTLD, suggesting that, besides Aβ pathway, the plasmin system may affect cognition through synaptic activity.

• MeSH
• biologické markery krev   MeSH
• frontotemporální lobární degenerace * krev   MeSH
• inhibitor aktivátoru plazminogenu 1 * krev   MeSH
• kognitivní dysfunkce krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• tkáňový aktivátor plazminogenu krev   metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Background: To evaluate the association between hypertriglyceridemic waist (HTGW), a promising marker of visceral adiposity and cardiovascular (CV) risk, and different indicators of vascular damage in type 2 diabetes (T2D) patients. Methods: This case-control study included 161 patients with T2D (91 males, 70 females) and 40 healthy controls (24 males, 16 females). HTWG was defined as waist circumference >90 cm in men or >85 cm in women and triglyceride concentrations >2 mmol/L. In addition to anthropometric and metabolic parameters, markers of endothelial dysfunction, namely von Willebrand factor (vWF) and plasminogen activator inhibitor-1 (PAI-1), were assessed. Arterial stiffness parameters were examined using the SphygmoCor system. Results: Individuals with T2D and HTGW showed the highest elevation of PAI-1 levels and significantly increased vWF levels compared with healthy controls. No significant differences in arterial stiffness markers were observed between T2D individuals. Age and, for several markers, systolic and/or diastolic blood pressure were identified as the main predictors for arterial stiffness, whereas PAI-1 and vWF levels were predicted by metabolic parameters. Conclusions: HTGW represents increased CV risk in T2D patients, mainly due to endothelial damage. The presence of HTGW had no significant effect on arterial stiffness compared with other T2D individuals.

• MeSH
• biologické markery krev   MeSH
• diabetes mellitus 2. typu * epidemiologie   MeSH
• hypertriglyceridemický pas * epidemiologie   MeSH
• inhibitor aktivátoru plazminogenu 1 krev   MeSH
• kardiovaskulární nemoci * krev   diagnóza   epidemiologie   MeSH
• lidé MeSH
• studie případů a kontrol MeSH
• von Willebrandův faktor analýza   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

To compare circulating pigment epithelium derived factor (PEDF) levels in type 2 diabetes patients (T2D) with and without metabolic syndrome (MetS+/-) to healthy controls and assess PEDF association with plasminogen activator inhibitor-1 (PAI-1) and von Willebrand factor (vWF) as markers of endothelial dysfunction. Fifty T2D individuals and forty healthy controls were included. PEDF, PAI-1, vWF, anthropological parameters, lipids, and markers of insulin resistance were investigated in all subjects. Compared to controls only MetS+ diabetics had higher PEDF levels [14.2 (10.2-16.0) mg/l vs. 11.1 (8.6-14.4) mg/l; p<0.05]. PEDF significantly correlated: positively with body mass index (rho=0.25), smoking (rho=0.21), C-reactive protein (rho=0.22), triglycerides (rho=0.38), non-HDL-cholesterol (rho=0.39), apolipoprotein B (rho=0.38), fasting glucose (rho=0.22), glycated hemoglobin (rho=0.24), C-peptide (rho=0.28), insulin (rho=0.26); and negatively with HDL-cholesterol (rho=-0.42) and apolipoprotein A1 (rho=-0.27). Independent association of PEDF with vWF in T2DMetS- subjects was found. Significantly elevated PEDF in T2DMet+ patients and its association with adverse metabolic profile confirmed PEDF as a marker of insulin resistance. Negative independent association of PEDF with vWF in T2DMetS- patients may reveal its angio-protective role.

• MeSH
• biologické markery krev   MeSH
• diabetes mellitus 2. typu krev   diagnóza   MeSH
• dospělí MeSH
• inhibitor aktivátoru plazminogenu 1 krev   MeSH
• inzulinová rezistence fyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neurotrofní faktory krev   MeSH
• oční proteiny krev   MeSH
• průřezové studie MeSH
• senioři MeSH
• serpiny krev   MeSH
• von Willebrandův faktor metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

x

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• MeSH
• antifosfolipidový syndrom diagnóza   MeSH
• dědičnost genetika   MeSH
• faktor VIII MeSH
• fibrin nedostatek   MeSH
• genetické testování MeSH
• inhibitor aktivátoru plazminogenu 1 krev   MeSH
• komplikace těhotenství MeSH
• lidé MeSH
• nedostatek proteinu C etiologie   farmakoterapie   patologie   MeSH
• nedostatek proteinu S MeSH
• protrombin MeSH
• rezistence k aktivovanému proteinu C etiologie   patologie   MeSH
• rizikové faktory MeSH
• tromboembolie prevence a kontrola   MeSH
• trombofilie * diagnóza   etiologie   klasifikace   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH

AIMS: Statins are known to influence the status of adipokines, which play a key role in the pathophysiology of cardiometabolic diseases. As the effect of ezetimibe as an add-on to statin therapy on the impact of statins on plasma adipokines levels is currently unclear, the aim of the present study was to investigate this through a meta-analysis of controlled trials. METHODS: A systematic review was performed, followed by a bibliographic search in PubMed, Medline, SCOPUS, Web of Science and Google Scholar databases. Quantitative data synthesis was performed using a fixed- or random-effects model (based on the level of interstudy heterogeneity) and the generic inverse variance weighting method. Effect sizes were expressed as standardized mean difference (SMD) and 95% confidence interval (CI). RESULTS: Meta-analysis of 23 controlled trials did not suggest any significant effect of adding ezetimibe on top of statin therapy on plasma concentrations of adiponectin (SMD 0.34, 95% CI -0.28, 0.96; P = 0.288), leptin (SMD -0.75, 95% CI: -2.35, 0.85; P = 0.360), plasminogen activator inhibitor 1 (SMD -1.06, 95% CI: -2.81, 0.69; P = 0.236) and interleukin 6 (SMD 0.30, 95% CI: -0.08, 0.67; P = 0.124). However, significantly greater reductions in plasma concentrations of tumour necrosis factor α (TNF-α) (SMD -0.48, 95% CI -0.87, -0.08; P = 0.018) were achieved with ezetimibe/statin combination therapy. CONCLUSIONS: The results suggested that ezetimibe add-on to statin therapy is associated with an enhanced TNF-α-lowering effect compared with statin monotherapy. Owing to the emerging role of TNF-α in the pathogenesis of metabolic disorders, further investigations are required to unveil the translational relevance of this TNF-α-lowering effect.

• MeSH
• adiponektin krev   MeSH
• anticholesteremika farmakologie   terapeutické užití   MeSH
• ateroskleróza krev   farmakoterapie   MeSH
• ezetimib farmakologie   terapeutické užití   MeSH
• inhibitor aktivátoru plazminogenu 1 krev   MeSH
• interleukin-6 krev   MeSH
• kombinovaná farmakoterapie metody   MeSH
• leptin krev   MeSH
• lidé MeSH
• randomizované kontrolované studie jako téma MeSH
• statiny farmakologie   terapeutické užití   MeSH
• TNF-alfa krev   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• přehledy MeSH
• srovnávací studie MeSH

BACKGROUND: Both apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) are accepted as alternative risk factors or targets for lipid-lowering therapy, which correlate more strongly with cardiovascular events than low-density lipoprotein cholesterol. OBJECTIVE: The aim of this cross-sectional study was to evaluate the differences in plasma levels of plasminogen activator inhibitor-1 (PAI-1) and of von Willebrand factor (vWF) as endothelial hemostatic markers and carotid intima-media thickness (C-IMT) as a morphologic marker for atherosclerotic vascular disease among dyslipidemic individuals with apoB levels higher, estimated or lower based on regression equation of apoB vs non-HDL-C. METHODS: A total of 594 dyslipidemic subjects without atherosclerotic manifestation were divided into 3 groups (according to tertiles of apoB levels above, within, and below the line of identity): H-apoB (n = 200), E-apoB (n = 194), and L-apoB (n = 200). PAI-1, vWF, C-IMT and lipids, anthropometric parameters, markers of insulin resistance, and inflammation were measured. Differences in variables between groups were analyzed using analysis of variance. RESULTS: There was a strong association between apoB and non-HDL-C. The correlations of apoB and of non-HDL-C with markers of endothelial damage and C-IMT were very similar. Despite these facts, individuals with higher apoB levels had significantly higher levels of PAI-1 compared with individuals with estimated (P < .05) or lower apoB (P < .001). There were no significant differences in vWF, C-IMT, markers of insulin resistance, obesity, and inflammation. CONCLUSION: Individuals with apoB higher than predicted by non-HDL-C had significantly higher levels of PAI-1, which may contribute to the increased risk of future atherothrombotic events.

• MeSH
• apolipoproteiny B krev   MeSH
• ateroskleróza krev   diagnostické zobrazování   patofyziologie   MeSH
• biologické markery metabolismus   MeSH
• dospělí MeSH
• dyslipidemie krev   diagnostické zobrazování   patofyziologie   MeSH
• endotel metabolismus   MeSH
• hemostáza * MeSH
• inhibitor aktivátoru plazminogenu 1 krev   MeSH
• intimomediální šíře tepenné stěny * MeSH
• LDL-cholesterol krev   MeSH
• lidé MeSH
• průřezové studie MeSH
• von Willebrandův faktor metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: The study aimed at finding a laboratory approach to detect endothelial damage in normal pregnancy as well as in pregnancy complicated by preeclampsia using selected markers of endothelial activation. MATERIALS: A total of 403 healthy pregnant women without a history of deep vein thrombosis and/or hypertension were prospectively studied. From all women, venous blood was collected before the end of the 1st trimester, between weeks 24 and 28 of gestation, and in the 3rd trimester (weeks 34-36). Assays of tissue plasminogen activator, plasminogen activator inhibitor-1, von Willebrand factor activity and antigen, thrombomodulin, endothelial protein C receptor, and endothelial microparticles activated by TF were performed. RESULTS: When comparing women who developed preeclampsia during pregnancy (the average levels were 23.41 mug/L, 34.33 mug/L, and 53.56 mug/L in the 1st, 2nd, and 3rd trimesters, respectively) with healthy pregnant women (the average levels were 19.05 mug/L, 28.47 mug/L, and 39.86 mug/L in the 1st, 2nd, and 3rd trimesters, respectively) significant differences in the levels of thrombomodulin were found in all three trimesters. By contrast, no statistically significant differences in the levels of vWF (both antigen and activity), t-PA, EPCR, EMPs, MMP-2, MMP-9, and TIMP-9 were found in any trimesters in the same group. CONCLUSIONS: Pregnancy and preeclampsia strongly influence the levels of studied markers. The findings of this work confirm the possible predictive potential of thrombomodulin and PA-1.

• MeSH
• biologické markery * krev   MeSH
• CD antigeny krev   MeSH
• cévní endotel patofyziologie   MeSH
• dospělí MeSH
• endoteliální receptor proteinu C MeSH
• inhibitor aktivátoru plazminogenu 1 krev   MeSH
• lidé MeSH
• mladý dospělý MeSH
• preeklampsie * krev   patofyziologie   MeSH
• prospektivní studie MeSH
• první trimestr těhotenství * krev   MeSH
• receptory buněčného povrchu krev   MeSH
• referenční hodnoty MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• tkáňový aktivátor plazminogenu krev   MeSH
• trombomodulin krev   MeSH
• von Willebrandův faktor metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH

BACKGROUND/AIMS: Oxidized low-density lipoprotein (oxLDL) in complex with β2-glycoprotein I (β2GPI) has been associated with autoimmune diseases, diabetes mellitus, chronic renal disease and coronary atherosclerosis. The aim of our study was to determine whether plasma levels of oxLDL/β2GPI complexes are associated with insulin resistance, inflammation and markers of endothelial damage in obese middle-aged men and, if so, whether oxLDL/β2GPI correlates better with insulin resistance parameters than oxLDL, advanced oxidation protein products (AOPP) or thioredoxin. METHODS: A total of 72 healthy men were recruited (41 obese and 31 nonobese individuals). Waist circumference >94 cm was used as the criterion for abdominal obesity. RESULTS: The obese men demonstrated higher oxLDL/β2GPI levels (p < 0.001), homeostasis model assessment of insulin resistance (p < 0.01) and intima-media thickness of the common carotid artery (p < 0.01). oxLDL/β2GPI correlated with more insulin resistance parameters compared to AOPP, thioredoxin or oxLDL. Furthermore, oxLDL/β2GPI was associated with plasminogen activator inhibitor-I (PAI-I; r = 0.365, p < 0.001) and negatively with interleukin-8 (r = -0.297, p < 0.05). CONCLUSIONS: In summary, oxLDL/β2GPI reflects the criterion for abdominal obesity and markers of insulin resistance in our study. The independent positive correlation with PAI-I indicates that oxLDL/β2GPI may serve as an early marker of low-grade inflammation and atherosclerosis initiation.

• MeSH
• abdominální obezita krev   patofyziologie   MeSH
• ateroskleróza krev   patofyziologie   MeSH
• beta-2-glykoprotein I krev   MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• inhibitor aktivátoru plazminogenu 1 krev   MeSH
• interleukin-8 krev   MeSH
• intimomediální šíře tepenné stěny MeSH
• inzulinová rezistence MeSH
• lidé středního věku MeSH
• lidé MeSH
• lipoproteiny LDL krev   MeSH
• multivariační analýza MeSH
• obvod pasu MeSH
• oxidační stres MeSH
• produkty pokročilé oxidace proteinů krev   MeSH
• regresní analýza MeSH
• studie případů a kontrol MeSH
• thioredoxiny krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Plasminogen activator ihnibitor (PAI 1) belongs to the plasminogen activator system, which is part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumors. Its plasma level is normally low but 4G/4G homozygotes have higher concentrations of PAI 1. This genotype may be associated with worse prognosis and proximal location of colorectal cancer than 5G/5G homozygotes. In our prospective evaluation we examined plasma level PAI 1 (using photometric microplate method ELISA) pre-surgery and, subsequently, 6-8 weeks later, from 80 patients. For the PAI 1 rs1799889 -675 4G/5G polymorphism test the PCR amplification was used.Analysis of collected data was confirmed that significantly higher plasma levels of PAI 1 were found in patients before starting therapy, which decreased (p=0.004) after initiation of treatment. Patients with higher plasma level PAI 1 before (p=0.013) and after therapy (p=0.004) had significantly shorter survival. We found no relationship between polymorphisms of PAI 1 (-675 4G/5G) in relation to stage, survival or tumor location. PAI 1 is useful as a negative marker of prognosis and could be advantageous when planning adjuvant treatment of patients with colorectal carcinoma. Although opinions on the importance of polymorphisms of PAI 1 in relation to the prognosis are not uniform, it does seem that their role in the prognosis of patients with colorectal cancer is not essential.

• MeSH
• genotyp MeSH
• inhibitor aktivátoru plazminogenu 1 krev   genetika   MeSH
• kolorektální nádory genetika   mortalita   MeSH
• lidé MeSH
• polymorfismus genetický * MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND/AIMS: Urokinase (uPA) is a serine protease, which together with uPAR, tPA, PAI 1 and PAI 2 forms the plasminogen activator system, a component of metastatic cascade contributing to the invasive growth and angiogenesis of malignant tumours. METHODOLOGY: Both preceding therapy and after 6-8 weeks of the treatment, plasma PAI 1 levels (photometric microplate method on the ELISA) and uPA, uPAR, PAI 1 and PAI 2 tissue expression (immunohistochemical reaction) were analysed from 80 colorectal carcinoma patients. RESULTS: Analysis showed higher pre-treatment plasma levels of PAI 1 in patients with advanced tumours, which decreased after surgery or the start of therapy (p=0.004); Patients with higher plasma level PAI 1 before (0.013) and after therapy (0.004) had significantly shorter survival. There was a higher expression of uPA (p<0.001), uPAR (p<0.001), PAI 1 (p=0.042) and PAI 2 (p<0.001) in advanced colorectal carcinoma. A relationship between PAI 2 (p=0.010) and uPAR (p=0.019) expression and survival was demonstrated. There is a correlation between pre-treatment plasma PAI 1 levels and PAI 2 (p=0.028) and uPAR (p=0.043) expression. CONCLUSIONS: Immunohistochemical analysis of PAS in tumour tissue and plasma PAI 1 levels was found to be a useful prognostic factor in colorectal carcinoma patients. Plasma PAI 1 could be advantageous in evaluating the effectiveness of a mode of treatment.

• MeSH
• aktivátor plazminogenu urokinázového typu analýza   MeSH
• dospělí MeSH
• imunohistochemie MeSH
• inhibitor aktivátoru plazminogenu 1 analýza   krev   MeSH
• inhibitor aktivátoru plazminogenu 2 analýza   MeSH
• kolorektální nádory metabolismus   mortalita   MeSH
• lidé středního věku MeSH
• lidé MeSH
• receptory urokinázového aktivátoru plazminogenu analýza   MeSH
• senioři nad 80 let MeSH
• senioři 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