Reduced DNA methylation the human kidney is associated with increased blood pressure

Background and aims: There is increasing evidence that epigenetic modifications such as DNA methylation (addition of a methyl group to DNA (5mC) that leads to altered gene expression) is important to the development of common complex cardiovascular diseases. A recent study found that DNA methylation of blood cells is associated with blood pressure (BP). So far there has been no studies of epigenetic changes in the kidney, which is a key organ in BP regulation and the development of hypertension. The aim of this study was to examine associations between BP and the global methylation profiles of the kidney and blood. Methods and results: We used 93 human renal tissue samples from the TRANScriptome of RenaL HumAN TissueE (TRANSLATE) Study. All samples were collected from healthy, unaffected by cancer pole of the kidney after elective unilateral nephrectomies. DNA was extracted using the DNeasy Qiagen kit according to the protocol from blood and kidney samples. Global methylation was measured by ELISA assay to determine the percentage of 5mC in all DNA samples. A significant negative relationship was found between renal 5mC percentages and systolic (SBP) and diastolic (DBP) blood pressure (SBP r = -0.25, P = 0.018, DBP r = -0.32, P = 0.002). This correlation was also evident when BP is corrected for effects of antihypertensive medications (adjusted SBP P = 0.046, adjusted DBP P = 0.009). Comparatively, there was no significant relationship between 5mC percentage and BP in DNA extracted from peripheral blood leukocytes. Conclusions: We found a significant negative correlation between the percentage of 5mC and BP in the renal DNA samples indicating that reduced DNA methylation leads to increased blood pressure. No such relationship was established in the leukocyte DNA, indicating that blood may not be a good template for analysis of epigenetic modifications in the hypertensive population

The involvement of Kidney DNA methylation in blood pressure regulation

Background and aims: Increasing evidence suggests that epigenetic modifications such as DNA methylation (5mC) is important to the development of essential hypertension, and that changes in DNA methylation of blood cells is associated to blood pressure (BP). So far there has been no studies of epigenetic changes in the kidney - an important effector organ in BP regulation. The aim of this study was to compare the global and gene specific methylation status in the kidney between normal and hypertensive subjects. Methods and results: We used 96 human renal tissue samples from the TRANScriptome of RenaL HumAN TissueE (TRANSLATE) Study to measure DNA methylation. TRANSLATE consists of carefully characterised collections of “apparently healthy” specimens of human kidneys. DNA was extracted from peripheral blood leukocytes and kidney tissue using the DNeasy blood and tissue Qiagen kit. Global methylation was measured by ELISA assay to determine the percentage of 5mC and loci specific methylation status was determined using Infinium HumanMethylation 450K array (Illumina®, Australia). A significant negative relationship was found in the renal samples between 5mC% and systolic (SBP) and diastolic (DBP) blood pressure readings (SBP r=-0.25, P=<0.05), DBP r=-0.32, P=<0.01). This correlation was also evident when BP is adjusted for hypertensive medication effects (adjusted SBP P=<0.05, adjusted DBP P=<0.01). There was no significant relationship in DNA extracted from peripheral blood leukocytes between 5mC% and BP reading. We found 275 loci differentially methylated between hypertensive and normotensive individuals. Conclusions: DNA methylation is an important molecular mechanism for BP and hypertension in humans Maciej D Tomaszewski3, Fadi J Charchar4

Valorization of Sewage Sludge via Gasification and Transportation of Compressed Syngas

A significant challenge in the utilization of alternative gaseous fuels is to use their energy potential at the desired location, considering economic feasibility and sustainability. A potential solution is a compression, transportation in pressure tanks, and generation of electricity and heat directly at the recipient. In this research, the potential for generating syngas from abundant waste substrates was analyzed. The sewage sludge (SS) was used as an example of a bulky and abundant resource that could be valorized via gasification, compression, and transport to end-users in containers. A model was developed, and theoretical analyses were completed to examine the influence of the calorific value of the syngas produced from the SS gasification (under different temperatures and gasifying agents) on the efficiency of energy transportation of compressed syngas. First, the gasification simulation was carried out, assuming equilibrium in a downdraft gasifier (reactor) from 973–1473 K and five gasifying agents (O2, H2, CO2, water vapor, and air). Molar ratios of the gasifying agents to the (SS) C ranged from 0.1–1.0. The model predicted syngas composition, lower calorific values (LHV) for a given molar ratio of the gasification agent, and compressibility factor. It was shown that the highest LHV was obtained at 0.1 molar ratio for all gasifier agents. The highest LHV (~20 MJ∙(Nm3)−1) was obtained by gasification with H2 and the lowest (~13 MJ∙(Nm3)−1) in the case of air. Next, the available syngas volume in a compressed gas transportation unit and the stored energy was estimated. The largest syngas volume can be transported when O2 is used as a gasifying agent, but the highest amount of transported energy was estimated for gasification with H2. Finally, the techno-economic analyses showed that syngas from SS could be competitive when the energy of compressed syngas is compared with the demand of an average residential dwelling. The developed syngas energy transport system (SETS) concept proposes a new method to distribute compressed syngas in pressure tanks to end-users using all modes of transport carrying intermodal ISO containers. Future work should include the determination of energy demand for syngas compression, including pressure losses, heat losses, and analysis of the influence of syngas on storage and compression devices

Binding of SARS-CoV-2 and angiotensin-converting enzyme 2: clinical implications

No abstract available

Lead dependent tricuspid dysfunction: Analysis of the mechanism and management in patients referred for transvenous lead extraction

Background: Lead-dependent tricuspid dysfunction (LDTD) is one of important complicationsin patients with cardiac implantable electronic devices. However, this phenomenon isprobably underestimated because of an improper interpretation of its clinical symptoms. Theaim of this study was to identify LDTD mechanisms and management in patients referred fortransvenous lead extraction (TLE) due to lead-dependent complications.Methods: Data of 940 patients undergoing TLE in a single center from 2009 to 2011 wereassessed and 24 patients with LDTD were identifi ed. The general indications for TLE, pacingsystem types and lead dwell time in both study groups were comparatively analyzed. Theradiological and clinical effi cacy of TLE procedure was also assessed in both groups with precisionestimation of clinical status patients with LDTD (before and after TLE). Additionally,mechanisms, concomitant lead-dependent complications and degree (severity) of LDTD beforeand after the procedure were evaluated. Telephone follow-up of LDTD patients was performedat the mean time 1.5 years after TLE/replacement procedure.Results: The main indications for TLE in both groups were similar (apart from isolatedLDTD in 45.83% patients from group I). Patients with LDTD had more complex pacing systemswith more leads (2.04 in the LDTD group vs. 1.69 in the control group; p = 0.04). Therewere more unnecessary loops of lead in LDTD patients than in the control group (41.7% vs.5.24%; p = 0.001). There were no signifi cant differences in average time from implantationto extraction and the number of preceding procedures. Signifi cant tricuspid regurgitation(TR-grade III–IV) was found in 96% of LDTD patients, whereas stenosis with regurgitationin 4%. The 10% frequency of severe TR (not lead dependent) in the control group patients wasobserved. The main mechanism of LDTD was abnormal leafl et coaptation caused by: loop ofthe lead (42%), septal leafl et pulled toward the interventricular septum (37%) or too intensivelead impingement of the leafl ets (21%). LDTD patients were treated with TLE and reimplantationof the lead to the right ventricle (87.5%) or to the cardiac vein (4.2%), or surgery procedure with epicardial lead placement following ineffective TLE (8.3%). The radiological and clinicaleffi cacy of TLE procedure was very high and comparable between the groups I and II (91.7%vs. 94.2%; p = 0.6 and 100% vs. 98.4%; p = 0.46, respectively). Repeated echocardiographyshowed reduced severity of tricuspid valve dysfunction in 62.5% of LDTD patients. The follow--up interview confi rmed clinical improvement in 75% of patients (further improvement aftercardiosurgery in 2 patients was observed).Conclusions: LDTD is a diagnostic and therapeutic challenge. The main reason for LDTDwas abnormal leafl et coaptation caused by lead loop presence, or propping, or impingementthe leafl ets by the lead. Probably, TLE with lead reimplantation is a safe and effective optionin LDTD management. An alternative option is TLE with omitted tricuspid valve reimplantation.Cardiac surgery with epicardial lead placement should be reserved for patients withineffective previous procedures

Kidney DNA methylation as a driver of genetic change in the kidney

Objectives: Hypertension is associated with various physiological changes that result in an increased risk of stroke, cardiovascular events and chronic kidney disease. Here we conducted a genome-wide analysis of methylation changes in the human kidney to identify epigenetic signatures of hypertension using the largest collection of apparently healthy human renal tissue. As the first analysis of its kind in the human kidney we also determined whether these changes have functional consequences at the gene expression level. Methods: We examined DNA extracted from a total of 94 human kidneys to investigate methylation patterns in hypertension. We also examined RNA -sequencing to characterise the transcriptome of 180 human kidneys to uncover interactions between DNA methylation and gene expressi. Results: Our methylation analysis identified one hypertension-associated CpG site, three systolic blood pressure-associated CpG sites and 19 diastolic blood pressure -associated CpG sites; including four CpG sites previously identified in peripheral blood studies of hypertension. DNA methylation is a known regulator of gene expression; therefore, we investigated whether differential DNA methylation in proximity to hypertension-associated renal genes correlated with their renal expression. Methylation of two genes (FAM50B, PC) showed an association with renal expression. The transcriptome analysis of 180 kidneys revealed 14 hypertension-associated genes, 1 gene associated with systolic blood pressure and 6 genes associated with diastolic blood pressure; including those involved in smooth muscle response to blood pressure fluctuation and blood pressure response to salt intake in humans. Conclusion: Our study uncovered DNA methylation as a new regulatory mechanism underpinning hypertension-related changes in renal gene expression

The role of calcium score in evaluation of the advancing of ischemic heart disease

Introduction:  Thanks to development of technology, new noninvasive techniques of coronary arteries evaluation, such as Multislice Computed Tomography (MSCT) were introduced. Nowadays tomographs are characterized by spatial and time resolution sufficient for reliable assessment of coronary arteries. Moreover, the dose of radiation taken  by patient was substantially decreased. Two main methods of evaluation were introduced. Examination performed without contrast agent enables quantitive assessment of coronary arteries calcification by so called Agatston score. Another method performed after contrast injection is Computed Tomography Angiography (CTA)Goal: This studies purpose was to determine the role of Calcium Score in assessment of Coronary Arteries Disease (CAD) advancementMaterials and methods: In this studythe results of 100 consecutive patients (45% men, mean age 55 ± 8.9 years) were analyzed. All patients had a positive ECG stress test score. With a 64-row CT scan, coronary artery imaging of all patients was performed. The descriptive analysis of the group was based on information obtained from referrals issued by cardiologists to the MSCT. Analyzed parameters were: age, gender, indication for referral, Calcium Score and final diagnosis.Results: In most cases (84%) of patients with positive ECG stress test score, MSCT excluded significant changes in coronary arteries. Also, the correlation between Calcium Score and sex and diagnosis was proven.Conclusions: MSCT and Calcium Score enables to find patients without significant changes in coronary arteries and positive ECG stress test and to reduce the number of referrals to coronarography

Contributions of obesity to kidney health and disease: insights from Mendelian randomization and the human kidney transcriptomics

AIMS: Obesity and kidney diseases are common complex disorders with an increasing clinical and economic impact on healthcare around the globe. Our objective was to examine if modifiable anthropometric obesity indices show putatively causal association with kidney health and disease and highlight biological mechanisms of potential relevance to the association between obesity and the kidney. METHODS AND RESULTS: We performed observational, one-sample, two-sample Mendelian randomization (MR) and multivariable MR studies i