Cardiac fibrotization is a well-known process characteristic of many cardiac pathological conditions. The key element is excessive activation of cardiac fibroblasts, their transdifferentiation into myofibroblasts, increased production, and accumulation of extracellular matrix proteins, resulting in cardiac stiffness. The exact cellular mechanisms and molecular components involved in the process are not fully elucidated, but the SOCE mechanism could play an important role. Its key molecules are the molecular sensor of calcium in ER/SR - STIM and the highly selective calcium channels Orai located in the plasma membrane. This study aims to evaluate selected SOCE-associated genes in the activation of HCF cell culture by several known substances (phenylephrine, isoprenaline) that represent cardiovascular overload. After cell cultivation, cell medium was collected to measure the soluble collagen content. From the harvested cells, qRT-PCR was performed to determine the mRNA levels of the corresponding genes. The activation of cells was based on changes in the relative expression of collagen genes as well as the collagen content in the medium of the cell culture. We detected an increase in the expression of the Orai2 isoform, a change in the Orai1/Orai3 ratio and also an increase in the expression of the STIM2 isoform. These results suggest an increased activation of the SOCE mechanism under stress conditions of fibroblasts, which supports the hypothesis of fibroblast activation in pathological processes by altering calcium homeostasis through the SOCE mechanism.

• MeSH
• fibroblasty metabolismus   MeSH
• kanály aktivované uvolněním vápníku metabolismus   MeSH
• kultivované buňky MeSH
• lidé MeSH
• myokard cytologie   metabolismus   MeSH
• protein - isoformy metabolismus   MeSH
• proteiny STIM metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The stimulation of myocardium repair is restricted due to the limited understanding of heart regeneration. Interestingly, endogenous opioid peptides such as dynorphins and enkephalins are suggested to support this process. However, the mechanism-whether through the stimulation of the regenerative capacity of cardiac stem cells or through effects on other cell types in the heart-is still not completely understood. Thus, a model of the spontaneous cardiomyogenic differentiation of mouse embryonic stem (mES) cells via the formation of embryoid bodies was used to describe changes in the expression and localization of opioid receptors within cells during the differentiation process and the potential of the selected opioid peptides, dynorphin A and B, and methionin-enkephalins and leucin-enkephalins, to modulate cardiomyogenic differentiation in vitro. The expressions of both κ- and δ-opioid receptors significantly increased during mES cell differentiation. Moreover, their primary colocalization with the nucleus was followed by their growing presence on the cytoplasmic membrane with increasing mES cell differentiation status. Interestingly, dynorphin B enhanced the downregulation gene expression of Oct4 characteristic of the pluripotent phenotype. Further, dynorphin B also increased cardiomyocyte-specific Nkx2.5 gene expression. However, neither dynorphin A nor methionin-enkephalins and leucin-enkephalins exhibited any significant effects on the course of mES cell differentiation. In conclusion, despite the increased expression of opioid receptors and some enhancement of mES cell differentiation by dynorphin B, the overall data do not support the notion that opioid peptides have a significant potential to promote the spontaneous cardiomyogenesis of mES cells in vitro.

• MeSH
• buněčná diferenciace fyziologie   MeSH
• kardiomyocyty cytologie   fyziologie   MeSH
• myokard cytologie   MeSH
• myší embryonální kmenové buňky cytologie   metabolismus   MeSH
• myši MeSH
• opioidní peptidy metabolismus   MeSH
• receptory opiátové metabolismus   MeSH
• regenerace fyziologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Hypothermic incubation of chicken eggs leads to smaller embryos with enlarged hearts, originally described as hypertrophic. Over the years, however, accumulated evidence suggested that hyperplasia, rather than hypertrophy, is the predominant mechanism of cardiac growth during the prenatal period. We have thus set to re-evaluate the hypothermia model to precise the exact cellular mechanism behind cardiac enlargement. Fertilized chicken eggs were incubated at either 37.5 °C (normothermia) or 33.5 °C from embryonic day (ED) 13 onward (hypothermia). Sampling was performed at ED17, at which point wet embryo and heart weight were recorded, and the hearts were submitted to histological examination. In agreement with previous results, the hypothermic embryos were 29% smaller and had hearts 18% larger, translating into a 67% increase in the heart to body weight ratio (P < 0.05 for all parameters). The cell size was essentially the same between control and hypothermic hearts in all regions analysed. Likewise, there was no significant relationship between the cell size and heart weight; however, in the hypothermic hearts, there was a trend showing positive correlation between cell sizes in different cardiac regions and heart weight. Proliferation rate, determined on the basis of anti-phosphohistone H3 immunofluorescence, showed an overall increase in the hypothermic group, reaching statistical significance (P = 0.02, t-test) in the right ventricle. The proliferation rate was similar among different regions of the same heart. However, the correlation between the proliferation rate and heart weight was only small (r2 = 0.007 and r2 = 0.234 for the normothermic and hypothermic group, respectively). We thus conclude that hyperplasia is the predominant response mechanism in this volume-overload model; mechanistically, decreased heart rate at lower temperature increases the end-diastolic and stroke volume, minimizing the drop in cardiac output through the Frank- Starling mechanism.

• MeSH
• fluorescenční protilátková technika MeSH
• hyperplazie metabolismus   MeSH
• hypertrofie metabolismus   patofyziologie   MeSH
• kardiomyocyty MeSH
• kuřecí embryo MeSH
• myokard cytologie   metabolismus   MeSH
• proliferace buněk fyziologie   MeSH
• tepový objem fyziologie   MeSH
• terapeutická hypotermie metody   MeSH
• velikost orgánu fyziologie   MeSH
• zvířata MeSH
• Check Tag
• kuřecí embryo MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Human natural killer (HNK)-1 antibody is an established marker of developing cardiac conduction system (CCS) in birds and mammals. In our search for the evolutionary origin of the CCS, we tested this antibody in a variety of sauropsid species (Crocodylus niloticus, Varanus indicus, Pogona vitticeps, Pantherophis guttatus, Eublepharis macularius, Gallus gallus, and Coturnix japonica). Hearts of different species were collected at various stages of embryonic development and studied to map immunoreactivity in cardiac tissues. We performed detection on alternating serial paraffin sections using immunohistochemistry for smooth muscle actin or sarcomeric actin as myocardial markers, and HNK-1 to visualize overall staining pattern and then positivity in specific myocyte populations. We observed HNK-1 expression of various intensity distributed in the extracellular matrix and mesenchymal cell surface of cardiac cushions in most of the examined hearts. Strong staining was found in the cardiac nerve fibers and ganglia in all species. The myocardium of the sinus venosus and the atrioventricular canal exhibited transitory patterns of expression. In the Pogona and Crocodylus hearts, as well as in the Gallus and Coturnix ones, additional expression was detected in a subset of myocytes of the (inter)ventricular septum. These results support the use of HNK-1 as a conserved marker of the CCS and suggest that there is a rudimentary CCS present in developing reptilian hearts. Anat Rec, 302:69-82, 2019. © 2018 Wiley Periodicals, Inc.

• MeSH
• antigeny CD57 imunologie   metabolismus   MeSH
• biologické markery metabolismus   MeSH
• Coturnix embryologie   růst a vývoj   metabolismus   MeSH
• imunohistochemie MeSH
• monoklonální protilátky imunologie   MeSH
• myokard cytologie   metabolismus   MeSH
• počítačové zpracování obrazu metody   MeSH
• převodní systém srdeční anatomie a histologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

The aim of the study was to investigate the existence of valves in small peripheral coronary veins of porcine hearts. The study was performed on 20 porcine hearts using standard histological methods. The veins in the subepicardial and intramyocardial regions of the anterior and posterior parts of the interventricular septum and in the wall of the right atrium were studied. Valves were present in intramyocardial veins (diameter of 75-180 μm), in the veins located just beneath the external surface of the myocardium (diameter 120-170 μm) and in the terminal segments of the ventricular veins (diameter 250 μm) opening into the stems of the anterior interventricular vein and middle cardiac vein. Valves were also recorded in most veins of the subepicardial space. The described rich presence of valves in the small coronary veins may contribute to a better comprehension of their hemodynamic properties. These findings may also help to improve the understanding of the efficacy of retrograde application of medications, a novel technique in cardiology and cardiac surgery.

• MeSH
• koronární cévy anatomie a histologie   cytologie   MeSH
• myokard cytologie   MeSH
• prasata anatomie a histologie   MeSH
• srdeční chlopně anatomie a histologie   MeSH
• srdeční síně anatomie a histologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

This study is aimed to investigate whether simvastatin induces cardiomyocytes survival signaling in endotoxin (lipopolysaccharide, LSP)-induced myocardial injury, and if so, further to determine a role of survivin in simvastatin-anti-apoptotic effect. Wistar rats were pretreated with simvastatin (10-40 mg/kg po) before a single non-lethal dose of LPS. In myocardial tissue, LPS induced structural disorganization of myofibrils with significant inflammatory infiltrate (cardiac damage score, CDS = 3.87 ± 0.51, p < 0.05), whereas simvastatin dose-dependently abolished structural changes induced by LPS (p < 0.01). Simvastatin in 20 mg/kg and 40 mg/kg pretreatment, dose dependently, attenuated myocardial apoptosis determined as apoptotic index (28.8 ± 4.5% and 18.9 ± 3.5, p < 0.05), decreased cleaved caspase-3 expression (32.1 ± 5.8%, p < 0.01), along with significant Bcl-xL expression in the simvastatin groups (p < 0.01). Interestingly, in the simvastatin groups were determined significantly increased expression of survivin (p < 0.01), but in negative correlation with cleaved caspase-3 and apoptotic indices (p < 0.01). Simvastatin has a cardioprotective effects against LPS induced apoptosis. The effect may be mediated by up-regulation of survivin via activation of NF-κB, which leads to reduced activation of caspase-3 and consequent apoptosis of cardiomyocytes in experimental sepsis.

• MeSH
• aplikace orální MeSH
• apoptóza účinky léků   MeSH
• Escherichia coli MeSH
• kardiomyocyty účinky léků   patologie   MeSH
• kardiomyopatie etiologie   patologie   prevence a kontrola   MeSH
• kaspasa 3 metabolismus   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• lipopolysacharidy toxicita   MeSH
• modely nemocí na zvířatech MeSH
• myokard cytologie   patologie   MeSH
• potkani Wistar MeSH
• sepse komplikace   etiologie   MeSH
• signální transdukce účinky léků   MeSH
• simvastatin aplikace a dávkování   MeSH
• srdce účinky léků   MeSH
• statiny aplikace a dávkování   MeSH
• survivin metabolismus   MeSH
• transkripční faktor RelA metabolismus   MeSH
• upregulace účinky léků   MeSH
• viabilita buněk účinky léků   MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• dospělí MeSH
• experimenty na zvířatech MeSH
• hodnocení léčiv MeSH
• inzulinová rezistence imunologie   MeSH
• játra metabolismus   účinky léků   MeSH
• kombinovaná farmakoterapie * MeSH
• kyseliny mastné omega-3 * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• modely nemocí na zvířatech MeSH
• myokard cytologie   enzymologie   patologie   MeSH
• oxidační stres účinky léků   MeSH
• potkani inbrední SHR MeSH
• silymarin * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• statistika jako téma MeSH
• triglyceridy krev   metabolismus   škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• mužské pohlaví MeSH
• zvířata MeSH

• MeSH
• estrogeny farmakologie   MeSH
• ischemická choroba srdeční epidemiologie   patofyziologie   MeSH
• kardiomyocyty cytologie   patologie   účinky léků   MeSH
• lidé MeSH
• myokard * cytologie   metabolismus   MeSH
• pohlavní dimorfismus MeSH
• srdeční mitochondrie enzymologie   metabolismus   účinky léků   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH

Melatonin, a molecule involved in the regulation of circadian rhythms, has protective effects against myocardial injuries. However, its capability to regulate the maturation of cardiac progenitor cells is unclear. Recently, several studies have shown that melatonin inhibits the stabilization of hypoxia-inducible factors (HIFs), important signaling molecules with cardioprotective effects. In this study, by employing differentiating mouse embryonic stem cells, we report that melatonin significantly upregulated the expression of cardiac cell-specific markers (myosin heavy chains six and seven) as well as the percentage of myosin heavy chain-positive cells. Importantly, melatonin decreased HIF-1α stabilization and transcriptional activity and, in contrast, induced HIF-2α stabilization. Interestingly, the deletion of HIF-1α completely inhibited the pro-cardiomyogenic effect of melatonin as well as the melatonin-mediated HIF-2α stabilization. Moreover, melatonin increased Sirt-1 levels in a HIF-1α-dependent manner. Taken together, we provide new evidence of a time-specific inhibition of HIF-1α stabilization as an essential feature of melatonin-induced cardiomyogenesis and unexpected different roles of HIF-1α stabilization during various stages of cardiac development. These results uncover new mechanisms underlying the maturation of cardiac progenitor cells and can help in the development of novel strategies for using melatonin in cardiac regeneration therapy.

• MeSH
• faktor 1 indukovatelný hypoxií - podjednotka alfa metabolismus   MeSH
• melatonin farmakologie   MeSH
• myokard cytologie   metabolismus   MeSH
• myší embryonální kmenové buňky cytologie   metabolismus   MeSH
• myši MeSH
• stabilita proteinů účinky léků   MeSH
• vývoj svalů účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Coronary flow (CF) measured ex vivo is largely determined by capillary density that reflects angiogenic vessel formation in the heart in vivo. Here we exploit this relationship and show that CF in the rat is influenced by a locus on rat chromosome 2 that is also associated with cardiac capillary density. Mitochondrial tryptophanyl-tRNA synthetase (Wars2), encoding an L53F protein variant within the ATP-binding motif, is prioritized as the candidate at the locus by integrating genomic data sets. WARS2(L53F) has low enzyme activity and inhibition of WARS2 in endothelial cells reduces angiogenesis. In the zebrafish, inhibition of wars2 results in trunk vessel deficiencies, disordered endocardial-myocardial contact and impaired heart function. Inhibition of Wars2 in the rat causes cardiac angiogenesis defects and diminished cardiac capillary density. Our data demonstrate a pro-angiogenic function for Wars2 both within and outside the heart that may have translational relevance given the association of WARS2 with common human diseases.

• MeSH
• dánio pruhované MeSH
• embryo nesavčí MeSH
• endoteliální buňky pupečníkové žíly (lidské) cytologie   enzymologie   MeSH
• fyziologická neovaskularizace genetika   MeSH
• genetické lokusy MeSH
• genom * MeSH
• HEK293 buňky MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• malá interferující RNA genetika   metabolismus   MeSH
• mapování chromozomů MeSH
• mitochondrie genetika   metabolismus   MeSH
• myokard cytologie   enzymologie   MeSH
• savčí chromozomy chemie   MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• sekvenční seřazení MeSH
• signální transdukce MeSH
• tryptofan-tRNA-ligasa antagonisté a inhibitory   genetika   metabolismus   MeSH
• vývojová regulace genové exprese * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH