Cíl: Cílem studie bylo prozkoumat změny v expresi pro-zánětlivého a pro-apoptotického cytokinu tumor nekrotizující faktor alfa (TNFα) a mikroRNA (miRNA), které se podílejí na jeho regulaci v časném období po subarachnoidálním krvácení (SAK). Soubor a metodika: Exprese miRNA (miR-125b, miR-146a, miR-346, miR-155, miR-15b) a mRNA (TNFα) byly stanoveny pomocí kvantitativní polymerázové řetězové reakce v reálném čase z mozkové tkáně experimentálních zvířat. Celkem 88 zvířat bylo rozděleno do skupin Sham (kontrolní operace bez indukce SAK), Lehké SAK, Těžké SAK, do časových intervalů 2, 4, 6 a 8 h (n = 7 ve skupině); 4 zvířata byla použita jako absolutní kontrola. Výsledky: Byly nalezeny statisticky významné rozdíly v expresi TNFα mezi skupinami Sham a Těžké SAK ve všech zkoumaných časových intervalech (p < 0,05), dále mezi skupinami Sham a Lehké SAK 4 h po indukci SAK (p < 0,05) a mezi skupinami Lehké SAK a Těžké SAK ve 2 a 6h časovém intervalu (p < 0,05). Dále byl pozorován významný rozdíl v expresi miRNA-15b mezi skupinami Sham a Těžké SAK 8 h po začátku SAK (p < 0,05). U dalších analyzovaných miRNA jsme v expresi nepozorovali žádné statisticky významné změny. Závěr: SAK bylo asociováno s časným nárůstem exprese TNFα a miR-15b, zejména u skupiny Těžké SAK. Navzdory komplexitě vzájemné regulace mezi cytokiny a mikroRNA, může informace o časné aktivaci zánětlivých/apoptotických mechanismů několik hodin po SAK přispět k lepšímu poznání patofyziologie SAK. Pochopení mechanismů vzájemné regulace proapoptotických markerů TNFα a miR-15b může přispět ke zlepšení terapie této závažné patologie.

Aim: The aim of the study was to investigate expression changes of pro-inflammatory and pro-apoptotic cytokine tumor necrosis factor alpha (TNFα) and microRNAs (miRNAs) involved in its regulation in early pathophysiological changes after subarachnoid haemorrhage (SAH). Materials and methods: MiRNAs (miR-125b, miR-146a, miR-346, miR-155, miR-15b) and mRNA (TNFα) expression were determined by quantitative real-time polymerase chain reaction in brain tissue samples. A total of 88 animals were divided to Sham (control surgery without induction of SAH), Mild SAH, Severe SAH groups in following time-points: 2, 4, 6 and 8 h (n = 7 per group); including 4 animals used as an absolute control. Results: We have found a statistically significant difference in TNFα expression between Sham and Severe SAH groups at all the time-points (p < 0.05), between Sham and Mild SAH groups 4 h after induction of SAH (p < 0.05) and between Mild and Severe SAH groups at 2 and 6 h time-points (p < 0.05). Furthermore, a significant difference in miR-15b expression between Sham and Severe SAH groups was observed 8 h after SAH (p < 0.05). All the other microRNAs have not been significantly changed. Conclusions: SAH was associated with an early increase in TNFα and miR-15b expression especially in Severe SAH group. Despite complex cross-regulation between cytokines and miRNA, any information about the activation of inflammation/apoptotic mechanisms within a few hours after SAH may improve our knowledge of SAH pathophysiology. Furthermore, it can lead to therapeutic improvement using a combination of both pro-apoptotic markers TNFα and miR-15b.

• Klíčová slova
• časné poškození mozku, perforační model,
• MeSH
• apoptóza MeSH
• mikro RNA MeSH
• modely nemocí na zvířatech MeSH
• mozek patologie   MeSH
• potkani Sprague-Dawley MeSH
• subarachnoidální krvácení * patologie   MeSH
• zánět MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

• Publikační typ
• abstrakt z konference MeSH

• MeSH
• akutní nemoc MeSH
• biologické markery krev   MeSH
• cirkulující mikroRNA * krev   MeSH
• infarkt myokardu s elevacemi ST úseků patofyziologie   MeSH
• kardiogenní šok * patofyziologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• myokard metabolismus   MeSH
• prognóza MeSH
• senioři MeSH
• statistika jako téma MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• práce podpořená grantem MeSH

AIMS: The aim of this study was to investigate the relationship between gene Period3 (Per3) variable number tandem repeat (VNTR) polymorphism and chronic heart failure (CHF). METHODS: The study subjects (372 patients of Caucasian origin with CHF and 332 healthy controls) were genotyped for Per3 VNTR polymorphism using an allele-specific PCR. RESULTS: No significant differences in genotype or Per3 VNTR allele frequencies were found between CHF cases and controls (Pg=0.30, Pa=0.52). No significant differences were uncovered either between CHF cases according to etiology (DCMP vs. IHD; Pg=0.87, Pa=0.91). In the multivariate regression modeling, no predictive function of VNTR Per3 polymorphism on ejection fraction or NYHA class, hyperlipidaemia or type II diabetes risk was found. CONCLUSION: Per3 VNTR polymorphism is not a major risk factor for chronic heart failure or a factor modulating the severity of the CHF in this population.

• MeSH
• chronická nemoc MeSH
• cirkadiánní proteiny Period genetika   MeSH
• dospělí MeSH
• frekvence genu MeSH
• lidé středního věku MeSH
• lidé MeSH
• minisatelitní repetice * MeSH
• mladiství MeSH
• mladý dospělý MeSH
• polymorfismus genetický MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• srdeční selhání genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Matrix metalloproteinases (MMPs) as well as their inhibitors (TIMPs) play a crucial role in controlling extracellular matrix turnover and have recently been associated with atherosclerosis, myocardial and vascular injury. Moreover, the genetic variability of MMP genes has been suggested to play an important role in vascular remodeling and age-related arterial stiffening. This study aims to describe associations of 14 selected polymorphisms in genes for MMPs and TIMPs with selected cardiovascular parameters (including central pulse pressure), clinical conditions and drug treatment profiles in 411 stable ischemic patients with preserved systolic function of the left ventricle. The genotyping of 14 single-nucleotide polymorphisms in 8 genes was carried out either using 5´ exonuclease (TaqMan®) reagents or by restriction analysis. Numerous associations of the investigated polymorphisms with systolic and diastolic blood pressure, maximum left ventricular end diastolic pressure and ejection fraction were observed. While some of the observed effects were found to be age-dependent, associations with clinical conditions (hypertension, diabetes mellitus, angina pectoris) were only observed in women and associations with four groups of drugs (statins, nitrates, calcium channel blockers, anti-aggregation drugs) were only observed in men. The results of this study indicate that the genetic variability of MMPs and TIMPs is an important factor which influences cardiovascular functions and may have important consequences for individual therapy customization in the future.

• MeSH
• genetická variace MeSH
• ischemická choroba srdeční farmakoterapie   genetika   patofyziologie   MeSH
• kardiovaskulární látky terapeutické užití   MeSH
• krevní tlak * MeSH
• lidé MeSH
• matrixové metaloproteinasy genetika   MeSH
• tkáňové inhibitory metaloproteinas genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND AIM: The objective of this research was to determine whether invasively measured central pulse pressure (PP) in patients indicated for coronarography is associated with two common polymorphisms in the ACE2 region (rs4646156 and rs4646174). METHODS: A total of 307 patients were enrolled in the study. The genotyping of both SNPs from peripheral blood samples was carried out using 5'exonuclease (Taqman®) chemistry on the ABI Prism® 7000 system (Applied Biosystems, Foster City, CA, USA). RESULTS: In both polymorphisms, the associations with central PP were found to be highly significant when all five possible genotypes in the population had been compared (p = 0.0001). In men, there was a higher incidence of previous myocardial infarction in G0 genotype carriers of rs54646174 (OR ratio = 7; p = 0.005). The AA genotype of rs4646156 had a 7.81× higher risk of severe angina pectoris in women (OR = 7.81, p = 0.05). A significant difference in allelic frequency of ACE2rs4646174 was found between women with and without significant stenoses of the circumflex branch of the left coronary artery. CONCLUSION: More research into the role of ACE2 genetic variability in PP regulations is necessary for more detailed physiological and pathophysiological comprehension of PP regulation.

• MeSH
• angiotensin konvertující enzym genetika   MeSH
• demografie MeSH
• dospělí MeSH
• genetická predispozice k nemoci MeSH
• jednonukleotidový polymorfismus genetika   MeSH
• kardiovaskulární nemoci enzymologie   genetika   patofyziologie   radiografie   MeSH
• koronární angiografie * MeSH
• krevní tlak * MeSH
• lidé středního věku MeSH
• lidé MeSH
• multivariační analýza MeSH
• pulz 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

• MeSH
• cirkadiánní hodiny fyziologie   genetika   MeSH
• cirkadiánní rytmus * fyziologie   genetika   MeSH
• kardiovaskulární fyziologické jevy * MeSH
• lidé MeSH
• melatonin fyziologie   MeSH
• metabolismus fyziologie   genetika   MeSH
• poruchy cirkadiánního rytmu (spánek) MeSH
• proteiny CLOCK MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

BACKGROUND: Soluble ST2 (sST2) is an interleukin-33 receptor. sST2 was found to be an independent prognostic factor in patients with myocardial infarction, sepsis and heart failure. OBJECTIVES: To assess sST2 levels in patients with cardiogenic shock (CS) and septic shock (SS), and to evaluate the prognostic value of sST2 for short-term mortality. METHODS: The present prospective observational study evaluated 32 patients with CS, 17 patients with SS and 61 patients with ST segment elevation myocardial infarction (STEMI )(control group). Samples of serum were collected eight times and the follow-up time was three months. RESULTS: sST2 levels were elevated from admission in SS patients relative to patients with CS and STEMI, who exhibited peak sST2 levels 24 h after admission. On admission, CS patients had a median (5th percentile; 95th percentile) sST2 level of 62.5 pg/mL (8.3 pg/mL; 315.8 pg/mL) and SS patients had a median sST2 level of 216.4 pg/mL (46.8 pg/mL; 364.4 pg/mL). ROC analysis found sST2 to be a biomarker that could distinguish between CS and SS at admission (area under the curve [AUC] 0.813; P<0.01) with a cut-off value of 210.4 pg/mL. Patients with STEMI had significantly lower sST2 levels at admission (20.3 pg/mL (4.2 pg/mL; 339.8 pg/mL) compared with CS patients. The AUC of the ROC analysis was 0.671 (P=0.007) for the detection of CS in patients with STEMI. Only a weak correlation was observed between sST2 and B-type natriuretic peptide (r=0.376, P=0.05) and sST2 and N-terminal pro-B-type natriuretic peptide (r=0.496, P=0.019). No statistically significant differences were observed in sST2 levels in patients with CS and SS relative to three-month mortality. CONCLUSION: Levels of sST2 at admission are significantly higher in patients with SS compared with CS. sST2 could be a diagnostic marker to distinguish SS and CS as well as CS and STEMI at the time of admission. Levels of sST2 are related to levels of natriuretic peptides in CS but not in SS. sST2 levels are not a suitable prognostic marker for patients with CS and SS.

• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH