Expression data from pregnant rat hearts
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE30308 | GEO | 2015/06/12
SECONDARY ACCESSION(S): PRJNA143575
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.
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Project description:Hyperhomocysteinemia (HHCy) has been established as a risk factor for development of cardiovascular disease. Previous studies have focused on the alterations in vascular biology such as vasodilation and white cell infiltration. We have shown that in rats and mice with HHCy, superoxide reduces the ability of NO to regulate mitochondrial function. Molecular mechanisms responsible for HHCy changes in cardiac function and myocardial metabolism are not yet understood. This study was undertaken to determine the global changes in cardiac gene expression in dogs with chronic HHCy using Affymetrix Canine Array. Keywords: Disease state analysis
2006-12-31 | GSE5260 | 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.
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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.
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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.
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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.
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Project description:Hyperhomocysteinemia (HHcy) inhibits growth and is cytotoxic to bacterial, yeast, and mammalian cells. The aim of this study was to determine the changes in proteome of the yeast induced by HHcy and map N-homocysteinylated sites. We identified 38 up- and 32-down-regulated proteins as well as 244 N-homocysteinylation sites in 98 proteins in Saccharomyces cerevisiae; with 57 sites in 34 proteins occurring in vivo. The bioinformatics analysis indicated that the N-homocysteinylated proteins were involved in a wide range of cellular functions with mostly cytosolic and ribosomal localizations. Furthermore, we discovered that lysine N-homocysteinylation sites are surrounded by neutral, hydrophobic and buried amino acid residues, and 60% of them occur within helix. The KEGG enrichment pathway analysis of these N-Hcy-proteins suggested that N-homocysteinylation disrupts metabolism of amino acids, ribosome biogenesis and glycolysis/gluconeogenesis. These findings suggest that protein N-homocysteinylation and dysregulation of cellular proteostasis affecting ribosomal proteins, biosynthesis of amino acids and changes in basic cellular pathways signaling are involved in the toxicity of HHcy in yeast. Homologous proteins are likely to be involved in HHcy toxicity in human and animal cells. We believe that the collection of N-homocysteinylation sites presented here is an important resource for future functional studies of N-homocysteinylation in yeast.
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Project description:Hyperhomocysteinemia (HHcy) inhibits growth and is cytotoxic to bacterial, yeast, and mammalian cells. The aim of this study was to determine the changes in proteome of the yeast induced by HHcy and map N-homocysteinylated sites. We identified 38 up- and 32-down-regulated proteins as well as 244 N-homocysteinylation sites in 98 proteins in Saccharomyces cerevisiae; with 57 sites in 34 proteins occurring in vivo. The bioinformatics analysis indicated that the N-homocysteinylated proteins were involved in a wide range of cellular functions with mostly cytosolic and ribosomal localizations. Furthermore, we discovered that lysine N-homocysteinylation sites are surrounded by neutral, hydrophobic and buried amino acid residues, and 60% of them occur within helix. The KEGG enrichment pathway analysis of these N-Hcy-proteins suggested that N-homocysteinylation disrupts metabolism of amino acids, ribosome biogenesis and glycolysis/gluconeogenesis. These findings suggest that protein N-homocysteinylation and dysregulation of cellular proteostasis affecting ribosomal proteins, biosynthesis of amino acids and changes in basic cellular pathways signaling are involved in the toxicity of HHcy in yeast. Homologous proteins are likely to be involved in HHcy toxicity in human and animal cells. We believe that the collection of N-homocysteinylation sites presented here is an important resource for future functional studies of N-homocysteinylation in yeast.
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