Oviductal Glycoprotein 1 Promotes Hypertension by Inducing Vascular Remodeling through an Interaction with MYH9
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ABSTRACT:
PROVIDER: PRJNA848406 | ENA |
REPOSITORIES: ENA
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Project description:Hypertension is a common cardiovascular disease that is related to genetic and environmental factors, but its mechanisms remain unclear. DNA methylation, a classical epigenetic modification, not only regulates gene expression but is also susceptible to environmental factors, linking environmental factors to genetic modification. Therefore, globally screening differential genomic DNA methylation in hypertensive patients is important for investigating novel hypertension mechanisms.Differential genomic DNA methylation in hypertensive, prehypertensive, and healthy control individuals was screened using the Illumina 450K BeadChip and verified by pyrosequencing. Plasma oviduct glycoprotein 1 (OVGP1) levels were determined using an enzyme-linked immunosorbent assay. Ovgp1 transgenic and knockout mice were generated to analyze the function of OVGP1. The blood pressure levels of the mouse models were measured using the tail-cuff system and radiotelemetry methods. The role of OVGP1 in vascular remodeling was determined by vascular relaxation studies. Protein–protein interactions were investigated using a pull-down/mass spectrometry assay and verified with coimmunoprecipitation and pull-down assays. We found a hypomethylated site at cg20823859 in the promoter region of OVGP1, and the plasma OVGP1 levels were significantly increased in hypertensive patients. This finding indicates that OVGP1 is associated with hypertension. In Ovgp1 transgenic mice, OVGP1 overexpression caused an increase in blood pressure, dysfunctional vasoconstriction and vasodilatation, remodeling of arterial walls, and increased vascular superoxide stress and inflammation, and these phenomena were exacerbated by angiotensin II infusion. In contrast, Ovgp1 deficiency attenuated angiotensin II-induced vascular oxidase stress, inflammation, and collagen deposition. These findings indicate that OVGP1 is a prohypertensive factor that directly promotes vascular remodeling. Pull-down and coimmunoprecipitation assays showed that myosin heavy chain II-A (MYH9) interacted with OVGP1, whereas inhibition of MYH9 attenuated OVGP1-induced hypertension and vascular remodeling. CONCLUSIONS: Hypomethylation at cg20823859 in the promoter region of OVGP1 is associated with hypertension and induces upregulation of OVGP1. The interaction between OVGP1 and MYH9 contributes to vascular remodeling and dysfunction. Therefore, OVGP1 is a prohypertensive factor that promotes vascular remodeling by binding with MYH9.
2022-06-12 | GSE205952 | GEO
Project description:Hypoxia can induce vasoconstriction followed by vascular remodeling including hypertrophy and hyperplasia of pulmonary vascular smooth muscle and proliferation of endothelial cells. The goal of this project is to elucidate the genes involved in vascular remodeling following pulmonary hypertension. Total RNA was isolated from lungs of normoxic and hypoxic treated animals. Keywords: other
2003-07-16 | GSE482 | GEO
Project description:<p>Arterial stiffening is a hallmark of early vascular aging (EVA) syndrome and an independent predictor of cardiovascular morbidity and mortality. In this case-control study we sought to identify plasma metabolites associated with EVA syndrome in the setting of hypertension. An untargeted metabolomic approach was used to identify plasma metabolites in an age-, BMI- and sex-matched groups of EVA (n = 79) and non-EVA (n = 73) individuals with hypertension. After raw data processing and filtration, 497 putative compounds were characterized, out of which 4 were identified as lysophosphaditylcholines (LPCs) [LPC (18:2), LPC (16:0), LPC (18:0) and LPC (18:1)]. A main finding of this study shows that identified LPCs were independently associated with EVA status. Although LPCs have been shown previously to be positively associated with inflammation and atherosclerosis, we observed that hypertensive individuals characterized by 4 down-regulated LPCs had 3.8 times higher risk of EVA compared to those with higher LPC levels (OR = 3.8, 95% CI 1.7 – 8.5, P < .001). Our results provide new insights into a metabolomic phenotype of vascular aging and warrants further investigation of negative association of LPCs with EVA status. This study suggests that LPCs are potential candidates to be considered for further evaluation and validation as predictors of EVA in patients with hypertension </p>
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Project description:Fisher male Cyp1a1mRen2 rats were allocated into four groups of four biological replicates each: control; streptozotocin-induced diabetes alone; indole-3-carbinol induced hypertension alone; combined induced diabetes and hypertension. <br>Kidneys were harvested for microarray analysis.analysis.
2011-12-31 | E-MEXP-3165 | biostudies-arrayexpress
Project description:The mammalian oviduct is a complex, fibromuscular organ known for its role in orchestrating a series of timely and dynamic changes to suitably support early embryogenesis. Establishing successful reproductive outcomes are largely determined through effective and cohesive communication systems between the transient embryo and the maternal environment. Climate change-induced, Heat stress (HS), is one of the largest single stressors compromising reproductive function. Systemic changes in the redox status of the maternal environment, adversely affect fertilization and early embryonic development, negative causation of HS. Oviductal organoids represent a 3-dimensional, biomimetic model to study the physiological impact of HS on the physiology of the oviduct and the subsequent developing embryo. In this study, we aimed to generate a robust bovine oviductal organoid culture system to decrypt the oviducts' differential transcriptomic response to HS, to elucidate the impact of thermal stress on oviductal physiology with subsequent potential impacts on early embryo development.
2023-10-27 | GSE221929 | GEO
Project description:The mammalian oviduct is a complex, fibromuscular organ known for its role in orchestrating a series of timely and dynamic changes to suitably support early embryogenesis. Establishing successful reproductive outcomes are largely determined through effective and cohesive communication systems between the transient embryo and the maternal environment. Climate change-induced, Heat stress (HS), is one of the largest single stressors compromising reproductive function. Systemic changes in the redox status of the maternal environment, adversely affect fertilization and early embryonic development, negative causation of HS. Oviductal organoids represent a 3-dimensional, biomimetic model to study the physiological impact of HS on the physiology of the oviduct and the subsequent developing embryo. In this study, we aimed to generate a robust bovine oviductal organoid culture system to decrypt the oviducts' differential response to HS in terms of secreted EV-miRNome, to elucidate the impact of thermal stress on oviductal physiology with subsequent potential impacts on early embryo development.
2023-10-27 | GSE221895 | GEO
Project description:To investigate the underlying mechanism of pulmonary hypertension, the model of monocrotaline (MCT)-treated pulmonary arterial hypertension (PAH) rats were constructed to detect the differentially expressed profile of genes in lung tissue of PAH rat.
2024-01-11 | GSE252564 | GEO
Project description:The success of the early reproductive events depends on an appropriate communication between gametes/embryos and the oviduct. Extracellular vesicles (EVs) contained in oviductal secretions have been suggested as new players in mediating this crucial cross-talk by transferring their cargo (e.g. proteins, mRNA and small ncRNA) from cell to cell. However, little is known about the oviduct EVs composition and their implications in reproductive success. The objective of our study was to determine the changes of oviductal EVs mRNA content under the hormonal influence during the estrous cycle. Methods: EVs, exosomes and microvesicles, were isolated from bovine oviductal fluid at different stages of the estrous cycle (postovulatory-stage, early luteal phase, late luteal phase and pre-ovulatory stage). Total RNA was isolated and used for the preparation of RNA-seq libraries. RNA-sequencing was performed on an Illumina HiSeq 2500. The obtained sequence reads that passed quality filters were mapped to the bovine genome sequence using Hisat 2. Read counts were calculated with QuasR Qcount and statistical analysis with EdgeR to identify differential mRNA abundance across the different stages of the estrous cycle. Results: RNA-sequencing identified 903 differentially expressed transcripts (FDR<0.001) in bovine oviductal EVs across the estrous cycle. Major differences were found between post-ovulatory and the rest of the stages analyzed.Functional annotation of the differentially abundant mRNAs identified functions related to cilia expression, exosome/vesicles, and many transcripts encoding ribosomal proteins. Conclusions: Our findings represent the first extensive oviductal signature of bovine oviductal EVs mRNA content and contribute to a better understanding of the role of EVs as modulators of gamete/embryo-maternal interactions.
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Project description:Persistent liver injury triggers a fibrogenic program that causes pathologic remodelling of the hepatic microenvironment (i.e., liver fibrosis) and portal hypertension. The dynamics of gene regulation during liver disease progression and regression remain understudied. Here, we generated hepatic transcriptome profiles in two well-established liver disease models at peak fibrosis and during spontaneous regression after the removal of the inducing agents. We linked the dynamics of key liver disease readouts, such as portal pressure, collagen proportionate area, and transaminase serum levels, to most differentially expressed genes, enabling the identification of transcriptomic signatures of progressive vs. regressive liver fibrosis and portal hypertension. These candidate biomarkers (e.g., Scube1, Tcf4, Src, Hmga1, Trem2, Mafk, Mmp7) were also validated in RNA-seq datasets of patients with cirrhosis and portal hypertension. Finally, deconvolution analysis identified major cell types and suggested an association of macrophage and portal hepatocyte signatures with portal hypertension and fibrosis area in both models.
2024-02-13 | E-MTAB-13804 | biostudies-arrayexpress
Project description:Pulmonary arterial hypertension (PAH) is a fatal disease characterized by a progressive increase in pulmonary artery pressure caused by pathological pulmonary artery remodeling. Here, we show that endothelial cell (EC) senescence plays a negative role in pulmonary hypertension via juxtacrine interaction with smooth muscle cells (SMCs). By using EC-specific progeroid mice that we recently generated, we discovered that EC progeria deteriorated vascular remodeling in the lungs, and exacerbated pulmonary hypertension in mice exposed to chronic hypoxia. Mechanistically, senescent ECs overexpressed Notch ligands, which resulted in increased Notch signaling and activated proliferation and migration capacities in neighboring SMCs. Pharmacological inhibition of Notch signaling reduced the effects of senescent ECs on SMCs functions in vitro, and improved the worsened pulmonary hypertension in EC-specific progeroid mice in vivo. Our findings show that EC senescence is a critical disease-modifying factor in PAH and that EC-mediated Notch signaling is a pharmacotherapeutic target for the treatment of PAH, particularly in the elderly.
2023-04-30 | GSE228491 | GEO