Endothelin-1 (ET-1) induces pulmonary vascular remodeling and pulmonary hypertension secondary to pulmonary fibrosis. Given that endothelial cells are the main source of ET-1 and ET-1 from other cells may encounter difficulty penetrating vascular compartments, we hypothesize that endothelial-derived ET-1 promotes vascular remodeling secondary to pulmonary fibrosis. We used vascular endothelial ET-1 knock-out (VEETKO) and Wild type mice for this research. They were given intratracheal bleomycin and euthanized at day 28. We quantified pulmonary fibrosis, measured lung ET-1 and its receptors’ expression, and assessed pulmonary vascular remodeling by calculating medial wall index, muscularization index, adventitial collagen and adventitial fibroblast and macrophage accumulation. Right ventricle remodeling was also assessed. Both VEETKO and Wild type mice developed comparable pulmonary fibrosis and similar fibrosis-related gene expression. Compared to Wild type mice, bleomycin-induced VEETKO mice had lower ET-1 peptide levels (15.4 pg/mg vs. 31.2 pg/mg, p<0.01). Expression of both ET-1 receptors mRNAs were increased in fibrosis models. Bleomycin-induced fibrosis VEETKO mice had significantly less muscularized arterioles, lower muscularization index and attenuated adventitial collagen, fibroblast and macrophage accumulation as compared to that of Wild type mice. Right ventricular pressure, hypertrophy and fibrosis did not increase both in VEETKO and Wild type mice despite the more enhanced vascular remodeling in Wild type. In conclusion, endothelialderived endothelin-1 promotes pulmonary vascular remodeling secondary to bleomycin-induced pulmonary fibrosis., A. B. Hartopo, N. Arfian, K. Nakayama, Y. Suzuki, K. Yagi, N. Emoto., and Seznam literatury
Hypertension in obesity is associated with increased insulin resistance, vascular mass and body mass index (BMI). The purpose of the study was to visualize endothelin-1 (ET-1) mediated constriction in arteries isolated from subcutaneous adipose tissue from obese hypertensive women previously operated by gastric bypass. Functional studies were conducted in a microvascular myograph. Expressed as percentage of contraction elicited by 124 mM KCl concentration-response curves for ET-1 were shifted leftward in arteries from obese hypertensive patients compared to healthy normotensive subjects. The vasodilator response to the ET-1 antagonist BQ123 (1 μM) was significantly higher in arteries from obese hypertensive patients (p<0.001). BQ123 induced relaxation was inhibited by NO synthase inhibitor L-NAME (0.1 nM). Preincubation with BQ123 enhanced the relaxation induced by acetylcholine (ACh; 0.1 nM - 0.1 mM) (p<0.001), but not that induced by NO donor sodium nitroprusside (SNP; 0.1 nM - 0.1 mM), in arteries from obese hypertensive patients. The present study show that hypertension yet prevail after gastric bypass surgery and the ETA receptor antagonist BQ123 may be a useful tool in reducing blood pressure in obese hypertensive patients., K. Gradin, B. Persson., and Seznam literatury
The global epidemic of diabetes is of significant concern. Diabetes associated vascular disease signifies the principal cause of morbidity and mortality in diabetic patients. It is also the most rapidly increasing risk factor for cognitive impairment, a silent disease that causes loss of creativity, productivity, and quality of life. Small vessel disease in the cerebral vasculature plays a major role in the pathogenesis of cognitive impairment in diabetes. Endothelin system, including endothelin-1 (ET-1) and the receptors (ETA and ETB), is a likely candidate that may be involved in many aspects of the diabetes cerebrovascular disease. In this review, we took a brain-centric approach and discussed the role of the ET system in cerebrovascular and cognitive dysfunction in diabetes., W. Li, Y. Abdul, R. Ward, A. Ergul., and Seznam literatury
Diabetes increases the risk and worsens the progression of cognitive impairment. The hippocampus is an important domain for learning and memory. We previously showed that endothelin-1 (ET-1) reduced diabetes-induced inflammation in hippocampal neurons, suggesting a neuroprotective effect. Given that neurons and endothelial cells within the neurovascular unit depend on each other for proper function, we investigated the effect of ET-1 on brain-derived neurotrophic factor (BDNF) synthesis, a key neurotrophin and prosurvival factor, in neuronal (HT22 hippocampal neurons) and brain microvascular endothelial (BMEC-5i) cells under normal and diabetes-mimicking (high glucose plus palmitate) conditions. Cells were treated with exogenous ET-1 or ET receptor antagonists including ETB receptor selective antagonist BQ788 (1 μM) or dual-receptor antagonist bosentan (10 μM). Mature (m)BDNF, proBDNF and caspase-3 levels were measured by Western blotting. Diabetic conditions reduced the prosurvival mBDNF/proBDNF ratio in both HT22 and BMEC-5i cells. Addition of exogenous ET-1 had no effect on the BDNF system in HT22 cells in diabetic conditions. Both HT22 and BMEC-5i cells had an increase in the mBDNF/proBDNF ratio when grown in diabetes-simulating conditions in the presence of endothelin receptor inhibition. These data suggest that blockade of ET-1 may provide neuroprotection to hippocampal cells through the modulation of the BDNF system., R. Ward, Y. Abdul, A. Ergul., and Seznam literatury
Endothelial cells (ECs) are primary targets of glucose-induced tissue damage. As a result of hyperglycemia, endothelin-1 (ET-1) is upregulated in organs affected by chronic diabetic complications. The objective of the present study was to identify novel transcriptional mechanisms that influence ET-1 regulation in diabetes. We carried out the investigation in microvascular ECs using multiple approaches. ECs were incubated with 5 mM glucose (NG) or 25 mM glucose (HG) and analyses for DNA methylation, histone methylation, or long non-coding RNA- mediated regulation of ET-1 mRNA were then performed. DNA methylation array analyses demonstrated the presence of hypomethylation in the proximal promoter and 5’ UTR/first exon regions of EDN1 following HG culture. Further, globally blocking DNA methylation or histone methylation significantly increased ET-1 mRNA expressions in both NG and HG-treated HRECs. While, knocking down the pathogenetic lncRNAs ANRIL, MALAT1, and ZFAS1 subsequently prevented the glucose-induced upregulation of ET-1 transcripts. Based on our past and present findings, we present a novel paradigm that reveals a complex web of epigenetic mechanisms regulating glucose-induced transcription of ET-1. Improving our understanding of such processes may lead to better targeted therapies., S. Biswas, B. Feng, A. Thomas, S. Chen, E. Aref-Eshghi, B. Sadikovic, S. Chakrabarti., and Seznam literatury
Jeden z problémů středoevropského eneolitu představuje pohřební ritus badenské kultury, vcelku dobře dokumentovaný ve východní části jejího rozšíření a o to hůře v oblasti západní, kam spadají i Čechy. Předmětem předloženého příspěvku je prezentace prvních uspokojivě dokumentovaných kostrových hrobů ze jmenované oblasti, které byly prozkoumány v Holubicích, okr. Praha-západ. Práce přináší kromě zevrubného vyhodnocení nálezové situace a všech získaných pramenů též soubor radiokarbonových dat. Dále je v ní řešena detailní chronologická pozice hrobů a míra jejich podobnosti s projevy pohřbívání v jiných oblastech rozšíření badenského komplexu. and One important issue in the central European Eneolithic is the Baden culture burial rite, which is documented quite well in the eastern part of its territory, though worse in the western region, including Bohemia. The subject of this article is the presentation of the first satisfactorily documented inhumation graves from the specified area investigated in Holubice in the Prague-západ district. In addition to a thorough evaluation of the find situation and all of the acquired sources, the article also provides a set of radiocarbon dates. The work establishes the detailed chronological position of the graves and the degree of their similarity to the manifestations of burials in other areas of the Baden complex.
Článek se zabývá chronologií eneolitických inhumací z prostoru Moravy na základě radiokarbonového datování. Datováno bylo celkem 17 jedinců pomocí 20 radiokarbonových dat, přičemž se jedná především o jedince bez hrobové výbavy, či jedince pocházející z problematických kontextů. Studie pokrývá zejména období starého eneolitu, méně pak střední a pozdní eneolit. K většině pojednávaných pohřbů jsou nově publikovány nálezové okolnosti a antropologické posudky. Na základě chronologické analýzy hrobů datovaných radiokarbonovým datováním lze přibližně definovat časový rozptyl jednotlivých způsobů pohřbívání na Moravě. Nejspolehlivěji lze datovat ploché hroby s jedinci v natažené poloze bez hrobových přídavků do ca 3800–3600 BC. and The article addresses the chronology of Eneolithic inhumation burials in Moravia based on radiocarbon dating. A total of 17 individuals were dated using 20 radiocarbon dates, primarily individuals without grave goods or individuals from problematic contexts. The study mainly covers the period of the Early Eneolithic, to a lesser extent the Middle and Late Eneolithic. The find contexts and anthropological assessments are newly published for most of the burials in question. Based on the chronological analysis of graves dated by radiocarbon dating, it is possible to approximately define the time dispersion of individual burial methods in Moravia. Flat graves with individuals in a stretched position without grave goods can be most reliably dated to about 3800–3600 BC.
Využitie kombinovaného systému na báze pyrolýzy biomasy, resp. triedeného komunálneho odpadu, v kombinácii s čistením exhalátov za pomoci elektrického výboja, poskytuje zaujímavú možnosť znižovania skleníkotvorného CO2 a súčasne rozvoja niektorých foriem obnoviteľných zdrojov energie. Testovaný pilotný systém z hľadiska veľkosti zodpovedá približne potrebám bežne stavaných rodinných domov., Marcela Morvová., and Obsahuje bibliografii