Hyperhomocysteinemia alters the cardiac substrate metabolism by impairing NO bioavailability through oxidative stress
Ontology highlight
ABSTRACT:
ORGANISM(S): Canis lupus familiaris
PROVIDER: GSE5260 | GEO | 2006/12/31
SECONDARY ACCESSION(S): PRJNA96363
REPOSITORIES: GEO
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Project description:Hyperhomocysteinemia (HHcy) causes cardiovascular dysfunction and is associated with many complications during pregnancy related to reduced NO bioactivity. The mechanisms of HHcy on the NO-dependent control of myocardial metabolism was compared with L-NAME, which directly inhibits NO bioavailability, treated animals. We used microarrays to detail the global programme of gene expression underlying hyperhomocysteinemia during pregnancy and identified distinct classes of differentially regulated genes. Female SD rats were mated with male SD rats. Methionine was used to generate hyperhomocysteinemia model. L-NAME was used to generate NO restricted model. After treatment, the left ventricles were harvested for RNA extraction and hybridization on Affymetrix microarrays.
2015-06-12 | E-GEOD-30308 | biostudies-arrayexpress
Project description:Hyperhomocysteinemia (HHcy) causes cardiovascular dysfunction and is associated with many complications during pregnancy related to reduced NO bioactivity. The mechanisms of HHcy on the NO-dependent control of myocardial metabolism was compared with L-NAME, which directly inhibits NO bioavailability, treated animals. We used microarrays to detail the global programme of gene expression underlying hyperhomocysteinemia during pregnancy and identified distinct classes of differentially regulated genes.
2015-06-12 | GSE30308 | GEO
Project description:Hyperhomocysteinemia (HHcy) is an established and potent independent risk factor for degenerative diseases, including cardiovascular disease (CVD), Alzheimer disease, type II diabetes mellitus, and chronic kidney disease. HHcy has been shown to inhibit proliferation and promote inflammatory responses in endothelial cells (EC), and impair endothelial function, a hallmark for vascular injury. However, metabolic processes and molecular mechanisms mediating HHcy-induced endothelial injury remains to be elucidated. This study examined the effects of HHcy on the expression of mRNA and microRNA (miRNA) in human aortic endothelial cells treated with a pathophysiologically relevant concentration of homocysteine (Hcy 500 μM). This is the first study to consider the effects of HHcy on both global mRNA and miRNA expression changes for mechanism identification. Molecular axes and biochemical processes identified in this study are useful not only for the understanding of mechanisms underlying HHcy-induced endothelial injury, but also for discovering therapeutic targets for CVD in general.
2021-05-29 | GSE175745 | GEO
Project description:Hyperhomocysteinemia (HHcy) is an established and potent independent risk factor for degenerative diseases, including cardiovascular disease (CVD), Alzheimer disease, type II diabetes mellitus, and chronic kidney disease. HHcy has been shown to inhibit proliferation and promote inflammatory responses in endothelial cells (EC), and impair endothelial function, a hallmark for vascular injury. However, metabolic processes and molecular mechanisms mediating HHcy-induced endothelial injury remains to be elucidated. This study examined the effects of HHcy on the expression of mRNA and microRNA (miRNA) in human aortic endothelial cells treated with a pathophysiologically relevant concentration of homocysteine (Hcy 500 μM). This is the first study to consider the effects of HHcy on both global mRNA and miRNA expression changes for mechanism identification. Molecular axes and biochemical processes identified in this study are useful not only for the understanding of mechanisms underlying HHcy-induced endothelial injury, but also for discovering therapeutic targets for CVD in general.
2021-05-29 | GSE175735 | GEO
Project description:The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n=4). The array data revealed that 797 genes were differentially expressed (P<0.01; fold change of at least ±2). 150 genes were expressed at significantly greater levels in diabetic dogs and 647 were significantly reduced.
2010-08-24 | GSE14887 | GEO
Project description:<p><strong>INTRODUCTION: </strong>Myxomatous mitral valve disease (MMVD) is the most common cardiac condition in adult dogs. The disease progresses over several years and affected dogs may develop congestive heart failure (HF). Research has shown that myocardial metabolism is altered in cardiac disease, leading to a reduction in b-oxidation of fatty acids and an increased dependence upon glycolysis.</p><p><strong>OBJECTIVES: </strong>This study aimed to evaluate whether a shift in substrate use occurs in canine patients with MMVD; a naturally occurring model of human disease.</p><p><strong>METHODS: </strong>Client-owned dogs were longitudinally evaluated at a research clinic in London, UK and paired serum samples were selected from visits when patients were in ACVIM stage B1: asymptomatic disease without cardiomegaly and stage C: HF. Samples were processed using ultra-performance liquid chromatography mass spectrometry and lipid profiles were compared using mixed effects models with false discovery rate adjustment. The effect of disease stage was evaluated with patient breed entered as a confounder. Features that significantly differed were screened for selection for annotation efforts using reference databases.</p><p><strong>RESULTS: </strong>Dogs in HF had altered concentrations of lipid species belonging to several classes previously associated with cardiovascular disease. Concentrations of certain acylcarnitines, phospholipids and sphingomyelins were increased after individuals had developed HF, whilst some ceramides and lysophosphatidylcholines decreased.</p><p><strong>CONCLUSION: </strong>The canine metabolome appears to change as MMVD progresses. Findings from this study suggest that in HF myocardial metabolism may be characterised by reduced beta-oxidation. This proposed explanation warrants further research.</p>
2022-03-31 | MTBLS716 | MetaboLights
Project description:Oligonucleotide microarray analysis of left ventricular tissues from 3 Great dane dogs with dilated cardiomyopathy and 3 control dogs was performed. Three hundred and twenty three differentially expressed transcripts were detected. The transcript demonstrating the highest degree of upregulation was FKBP12.6 (calstabin2) and the transcript with the greatest amount of down regulation was triadin. Both of these transcripts are critical to proper functioning of the cardiac ryanodine receptor. Abnormalities of both calstabin2 and triadin have been reported in humans with heart disease. Further investigation into the role of calstabin2 and triadin in canine cardiomyopathy is warranted, and the canine disease may serve as a model of human disease. Keywords: control vs diseased 3 controls and 3 affected
2010-04-09 | E-GEOD-16049 | biostudies-arrayexpress
Project description:Murine monocytes (MC) are classified into Ly6Chigh and Ly6Clow MC. Ly6Chigh MC is the pro-inflammatory subset and the counterpart of human CD14++CD16+ intermediate MC which contributes to systemic and tissue inflammation in various metabolic disorders, including hyperhomocysteinemia (HHcy). This study aims to explore molecule signaling mediating MC subset differentiation in HHcy and control mice.Mouse white blood cell were prepared from peripheral blood and stained with antibody against CD11b, Ly6G and Ly6C and subjected for flow cytometry cell sorting. CD11b+Ly6G- cells were selected as MC. MC subsets (CD11b+Ly6G-Ly6Chigh, and CD11b+Ly6G-Ly6Clow) were sorted based on Ly6C levels. The quantification of MC was used flow cytometry analysis for Ly6Chigh and Ly6Clow MC in CT and Cbs-/-. Then, 100 ng mRNA were obtained from 100,000 sorted cells of CT and Cbs-/- (HHcy) mice. Around 30 million reads were achived and 16,487 normalized genes per sample by mRNA-Seq analysis.
2021-02-02 | GSE165879 | GEO
Project description:Hyperhomocysteinemia (HHcy) is an independent risk factor for atherosclerosis. However, a comprehensive understanding of immune cells in HHcy-accelerated atherosclerotic aortas (HHcy-AA) and the underlying mechanisms are still lacking. In this study, single-cell RNA sequencing (scRNA-seq) analysis of aortas from three atherosclerotic models on ApoE-/- mice revealed 15 distinct immune cell clusters. Among them, B cells showed the most significant increase in the vessels of HHcy ApoE-/- mice compared with those in ApoE-/- mice fed a chow diet or western diet (WD). Further cell-cell contact reanalyses revealed that B cells, but not dendritic cells or macrophages, played a dominant role in the class II major histocompatibility complex (MHCII) signaling in HHcy-AA. Mechanistically, Hcy induced the nuclear translocation of pyruvate kinase M2 (PKM2) in B cells. Nuclear PKM2 interacted with and phosphorylated cyclic AMP-responsive element-binding protein 1 (CREB1), and then PKM2-CREB1 complex bound to promoter III of Ciita, a master transactivator of MHCII, and further induced MHCII expression. Adoptive transfer experiments demonstrated that nuclear PKM2-regulated B cell antigen presentation is essential for B cell-mediated T cell activation and atherogenesis. In summary, our study provides a comprehensive immune cell atlas of HHcy-AA, which is distinct with those in WD-fed ApoE-/- mice. MHCII-related antigen presentation may be the main function of aortic B cells. We also provide a novel perspective for the intervention in early development of atherosclerosis via the PKM2-CREB1-CIITA-MHCII axis in B cells, especially for HHcy-accelerated vascular inflammation.
2021-12-08 | GSE190220 | GEO
Project description:The global changes in cardiac gene expression in dogs with alloxan-induced diabetes were studied using Affymetrix Canine Array. Cardiac RNA was extracted from the control and DM (n=4). The array data revealed that 797 genes were differentially expressed (P<0.01; fold change of at least ±2). 150 genes were expressed at significantly greater levels in diabetic dogs and 647 were significantly reduced. Mongrel dogs (weighing 22-29 kg, n = 13) were chronically instrumented for measurements of systemic hemodynamics. The control hemodynamics were recorded 10-14 days after the surgery. After the control recording, the dogs were divided into two groups: one normal (n = 7) and the other diabetic (n = 6). In the diabetic group, the dogs were injected with alloxan monohydrate (40-60 mg/kg iv) over 1 min. Alloxan was prepared as a 5% solution in citrate buffer (pH 4-4.5). Only dogs with blood glucose >200 mg/dl (fasted for at least 16 h) on day 7 were included in the diabetic group. Before and after the development of diabetes, the dogs had free access to water. Systemic hemodynamics were measured again after 4-5 wk. All the microarray analysis were perormed after 4 weeks of alloxan injection.
2010-08-23 | E-GEOD-14887 | biostudies-arrayexpress