Genetics of Hypertension Associated Treatment Study (GenHAT) Genomic Background of Blood Pressure Response to Thiazide Diuretic in African Americans
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PROVIDER: PRJNA785064 | ENA |
REPOSITORIES: ENA
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Project description:Genetics of Hypertension Associated Treatment Study (GenHAT) Genomic Background of Blood Pressure Response to Thiazide Diuretic in African Americans
| PRJNA785063 | ENA
Project description:Resistant Hypertension in African Americans
| PRJNA80271 | ENA
Project description:<p>Resistant hypertension is defined as blood pressure that remains above goal in spite of the concurrent use of 3 antihypertensive agents of different classes or the concurrent use of 4 or more antihypertensive agents regardless of control. Its diagnosis is important for the identification of patients who are at high risk of having reversible causes of hypertension and/or patients who, because of persistently high blood pressure levels, may benefit from special diagnostic and therapeutic considerations. Resistant hypertension represents an extreme phenotype, thus, it has been predicted that genetic factors could play a larger role than for the general hypertensive population. Genetic assessments of patients with resistant hypertension have been limited. The current study assayed the exome of 91 African American patients with treatment resistant hypertension.</p>
| phs000442.v1.p1 | EGA
Project description:Abstract: Background and aims: Portal hypertension (PH) is the most frequent and severe clinical syndrome associated to chronic liver disease (CLD), defined by a pathological increase in the hepatic venous pressure gradient (HVPG). Considering the known mechanobiological effects of hydrostatic pressure and shear stress on endothelial cells, we hypothesized that PH could not only be a consequence of, but significantly influence the phenotype of liver sinusoidal endothelial cells (LSECs) during disease progression. The aim of this study was to investigate the effects of pathological hydrodynamic pressure on LSECs and to identify endothelial-derived biomarkers of PH. Methods: Primary LSECs were cultured under normal or increased hydrodynamic pressure within a pathophysiological range (1 vs 12 mmHg) using a microfluidic liver-on-a-chip device. RNAseq was used to identify pressure-sensitive genes, which were validated in liver biopsies from two independent cohorts of CLD patients with PH (n=73) vs subjects without PH (n=23). Biomarker discovery was performed in plasma from a third independent cohort of 64 patients (46 with PH vs 18 w/o). Results: Transcriptomic analysis revealed a marked deleterious effect of pathological pressure in LSECs and identified chromobox 7 (CBX7) as a key transcription factor diminished by pressure. Hepatic CBX7 downregulation was validated in patients with PH and significantly correlated with HVPG. MicroRNA 181a-5p was identified as pressure-induced upstream regulator of CBX7. Analysis of two downstream targets of CBX7, ECAD and SPINK1, were found increased in the bloodstream of patients with PH and were highly predictive of PH and clinically significant PH, with a sensitivity of 91.3% and 91.4% respectively. Conclusions: We describe the detrimental effects of increased hydrodynamic pressure on the sinusoidal endothelium, identify CBX7 as a pressure-sensitive transcription factor, and propose that the combination of two of its reported products could be used as plasma biomarkers of PH.
2023-05-10 | GSE181255 | GEO
Project description:Background: Hypertension is one of the most common metabolic diseases in the elderly and its pathogenesis is associated with microbiota dysbiosis. Recent evidence suggests that oral microbiota dysbiosis is also an important factor in the development of hypertension. However, the relationship between hypertension and oral flora in the elderly has not been adequately investigated. Objective: The aim of this cross-sectional study was to investigate the structure of the oral microbiota and its correlation with hypertension in elderly hypertensive patients. To provide new ideas for the prevention and treatment of hypertension. Methods: 206 subjects aged 60 ~ 89 years were selected and divided into normal (CON) and hypertensive (HTN) groups, according to the 2018 Chinese Guidelines for the Management of Hypertension. The oral microbiome composition of saliva samples was determined by 16S rRNA gene sequencing. Results: Although there was no significant difference in α and β diversity between the two groups, systolic and diastolic blood pressure were the most important factors influencing the structure of the oral microbiota. At the phylum level, the relative abundance of the spirochete phylum and the mutualistic bacterial phylum was higher in the HT group than in the CON group (p < 0.05). Diastolic blood pressure was negatively correlated with Streptococcus. Furthermore, we analyzed HTN patients with 120 mmHg<systolic blood pressure<160 mmHg and systolic blood pressure>160 mmHg separately and found that the abundance of Saccharibacteria_(TM7) was significantly increased in the HTN_2 group. Conclusions: Our study identified specific oral microbiota in elderly hypertensive patients, confirming the relationship between oral microbiota and hypertension. This enhances our understanding of the important role of oral microbiota in the pathogenesis of hypertension and accumulates more evidence for microbial involvement in the development of hypertension.
2024-09-17 | GSE277296 | GEO
Project description:Splenomegaly is caused by several pathological conditions, including portal hypertension, which is most frequently caused by chronic liver disease (e.g., liver cirrhosis). The detailed mechanisms through which portal pressure induces splenomegaly and the precise pathophysiological conditions in portal hypertension-induced splenomegaly remain to be fully elucidated. We used microarrays to identify the differential microRNA expression underlying the portal hypertension-induced splenomegaly.
2018-11-21 | GSE113612 | GEO
Project description:Splenomegaly is caused by several pathological conditions, including portal hypertension, which is most frequently caused by chronic liver disease (e.g., liver cirrhosis). The detailed mechanisms through which portal pressure induces splenomegaly and the precise pathophysiological conditions in portal hypertension-induced splenomegaly remain to be fully elucidated. We used microarrays to identify the differential gene expression underlying the portal hypertension-induced splenomegaly.
2018-11-21 | GSE113613 | GEO
Project description:Background: Venous hypertension is often present in advanced and in acute decompensated heart failure (HF). However, it is unclear whether high intravenous pressure can cause alterations in homeostasis by promoting inflammation and endothelial cell (EC) activation. We used an experimental model of acute, local venous hypertension to study the changes in circulating inflammatory mediators and EC phenotype that occur in response to biomechanical stress. Methods and Results: Twenty-four healthy subjects (14 men, age 35±2 years) were studied. Venous arm pressure was increased to ~30 mmHg above baseline level by inflating a tourniquet cuff around the dominant arm (test arm). Blood and endothelial cells (ECs) were sampled from test and control arm (lacking an inflated cuff) before and after 75 minutes of venous hypertension, using angiocatheters and endovascular wires. Magnetic beads coated with EC specific antibodies were used for EC separation; amplified mRNA was analyzed by Affymetrix HG-U133 2.0 Microarray. Plasma endothelin-1 (ET-1), interleukin-6 (IL-6), vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-X-C motif) ligand 2 (CXCL2) were significantly increased in the congested arm. 5,332 probe sets were differentially expressed in venous ECs before vs. after testing. Among the 143 probe sets that exhibited a significant absolute fold change >2, we identified several inflammatory mediators including ET-1, VCAM-1, and CXCL2. Conclusions: Acute experimental venous hypertension is sufficient to cause local increase in circulating inflammatory mediators and to activate venous ECs in healthy human subjects. Additional work is needed to determine the effect of venous hypertension in patients with established HF. 24 samples were analyzed from 12 patients. Each patient contributed 2 samples (1 prior to intervention and 1 after intervention). The pre-intervention sample serves as the control.
2013-12-04 | E-GEOD-38783 | biostudies-arrayexpress
Project description:Aims: Hypertension poses a significant challenge to vasculature homeostasis and stands as the most common cardiovascular disease in the world. Its effects are especially profound on vasculature-lining endothelial cells that are directly exposed to the effects of excess pressure. Here, we characterize the in vivo transcriptomic response of cardiac endothelial cells to hypertension using the spontaneous hypertension mouse model BPH/2J. Methods and results: Verification of defective endothelial function in the BPH/2J hypertensive mouse strain was followed by acute isolation of cardiac endothelial cells and transcriptional profiling using RNA sequencing. Gene profiles from normotensive BPN/3J mice were compared to hypertensive animals. We observed over 3000 transcriptional differences between groups including pathways consistent with the cardiac fibrosis found in hypertensive animals. Importantly, many of the fibrosis-linked genes also differ between juvenile pre-hypertensive and adult hypertensive BPH/2J mice, suggesting that these transcriptional differences are hypertension-related. We also show that blood pressure normalization with amlodipine resulted in a subset of genes reversing their expression pattern, supporting the hypertension-dependency of altered gene expression. Yet, other transcripts were recalcitrant to therapeutic intervention illuminating the possibility that hypertension may irreversibly alter some endothelial transcriptional patterns. Conclusions: Hypertension has a profound effect on both function and transcription of endothelial cells, the latter of which was only partially restored with normalization of blood pressure. This study represents one of the first to quantify how endothelial cells are reprogrammed at the molecular level in cardiovascular pathology and advances our understanding of the transcriptional events associated with endothelial dysfunction.
2018-04-09 | GSE104530 | GEO
Project description:Rationale: Schistosomiasis is one of the most common causes of pulmonary arterial hypertension worldwide, but the pathogenic mechanism by which the host inflammatory response contributes to vascular remodeling is unknown. We sought to identify signaling pathways that play protective or pathogenic roles in experimental Schistosoma-induced pulmonary vascular disease by whole-lung transcriptome analysis. Methods: Wildtype mice were experimentally exposed to S. mansoni ova by intraperitoneal sensitization followed by tail vein augmentation, and the phenotype assessed by right ventricular catheterization and tissue histology, RNA and protein analysis. Whole-lung transcriptome analysis by microarray and RNA sequencing was performed, the latter analyzed using 2 bioinformatic methods. Functional testing of the candidate IL-6 pathway was determined using IL6-knockout mice and the STAT3 inhibitor STI-201. Results: Wild-type mice exposed to S. mansoni had increased right ventricular systolic pressure and thickness of the pulmonary vascular media. Whole lung transcriptome analysis identified the IL6-STAT3-NFATc2 pathway as being upregulated, which was confirmed by PCR and immunostaining of lung tissue from S. mansoni-exposed mice and patients who died of the disease. Mice lacking IL6 or treated with STI-201 developed pulmonary hypertension associated with significant intima remodeling after exposure to S. mansoni. Conclusions: Whole lung transcriptome analysis identified upregulation of the IL6-STAT3-NFATc2 pathway, and IL6 signaling was found to be protective against Schistosoma-induced intimal remodeling. Affy Mouse ST1.0 chip used. Whole lung transcriptome of 3 mice with experimental Schistosoma-induced pulmonary hypertension, compared to 3 control mice. All mice on a C57Bl6/J background.
2013-07-16 | E-GEOD-48936 | biostudies-arrayexpress