Aberrant DNA methylation of hypothalamic angiotensin receptor in prenatal-programmed hypertension
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA488560 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Malnutrition during pregnancy, which causes prenatal exposure to excessive glucocorticoid, induces adverse metabolic programming leading to hypertension in offspring. Pregnant rats receiving a low-protein diet exhibited moderate downregulation of 11-beta-dehydrogenase isozyme 2, which inactivates corticosterone, in the placenta, resulting in prenatal exposure to excessive corticosterone. In offspring of pregnant rats receiving a low-protein diet or dexamethasone, mRNA expression of angiotensin receptor type 1a (Agtr1a) in the paraventricular nucleus (PVN) of the hypothalamus was upregulated, concurrent with reduced expression of DNA methyltransferase 3a (Dnmt3a), reduced binding of DNMT3a to the Agtr1a promoter, and DNA demethylation, suggesting hypothalamic Agtr1a expression is epigenetically modulated by excess glucocorticoid. Dexamethasone treatment of PVN cells downregulated DNMT3a while upregulating Agtr1a, and decreased DNMT3a binding and DNA demethylation at the Agtr1a promoter. Consistent with Agtr1a upregulation in the hypothalamus, salt loading increased BP in both types of offspring. Even without dexamethasone treatment, hypothalamic neuron-specific DNMT3a-deficient mice, in which Agtr1a was upregulated, exhibited salt-induced BP elevation. By contrast, dexamethasone-treated Agtr1a-deficient mice failed to show salt-induced BP elevation, despite reduced expression of DNMT3a. Thus, epigenetic modulation of hypothalamic angiotensin signaling contributes to salt-sensitive hypertension induced by prenatal glucocorticoid excess in offspring of mothers that are malnourished during pregnancy.
2018-11-30 | GSE119235 | GEO
Project description:Maternal malnutrition, which causes prenatal exposure to excessive glucocorticoid, induces adverse metabolic programming, leading to hypertension in offspring. In offspring of pregnant rats receiving a low-protein diet or dexamethasone, a synthetic glucocorticoid, mRNA expression of angiotensin receptor type 1a (Agtr1a) in the paraventricular nucleus (PVN) of the hypothalamus was upregulated, concurrent with reduced expression of DNA methyltransferase 3a (Dnmt3a), reduced binding of DNMT3a to the Agtr1a gene, and DNA demethylation. Salt loading increased BP in both types of offspring, suggesting that elevated hypothalamic Agtr1a expression is epigenetically modulated by excessive glucocorticoid and leads to adult-onset salt-sensitive hypertension. Consistent with this, dexamethasone treatment of PVN cells upregulated Agtr1a, while downregulating Dnmt3a, and decreased DNMT3a binding and DNA demethylation at the Agtr1a locus. In addition, Dnmt3a knockdown upregulated Agtr1a independently of dexamethasone. Hypothalamic neuron-specific Dnmt3a-deficient mice exhibited upregulation of Agtr1a in the PVN and salt-induced BP elevation without dexamethasone treatment. By contrast, dexamethasone-treated Agtr1a-deficient mice failed to show salt-induced BP elevation, despite reduced expression of Dnmt3a. Thus, epigenetic modulation of hypothalamic angiotensin signaling contributes to salt-sensitive hypertension induced by prenatal glucocorticoid excess in offspring of mothers that are malnourished during pregnancy.
| S-EPMC6238751 | biostudies-literature
Project description:Hypertension induced with chronic or acute angiotensin treatment in mouse
2005-01-01 | E-TIGR-11 | biostudies-arrayexpress
Project description:Hypertension induced with chronic or acute angiotensin treatment in mouse. Related experiment E-TIGR-11
2005-01-01 | E-TIGR-12 | biostudies-arrayexpress
Project description:We are investigating of role of RhoBTB1 in vascular smooth muscle cells. Restoring RhoBTB1 expression in mouse aorta reversed the established arterial stiffness but not hypertension caused by angiotensin II (Ang-II). To investigate the underlying mechanism by which RhoBTB1 reversed arterial stiffness, we performed bulk RNA-sequencing using aorta from four groups: control /RhoBTB1 transgenic mice treated with/without Ang-II.
2022-04-08 | GSE189003 | GEO
Project description:We hypothesized that angiotensin II (AngII) affects transcriptome in the vasculature in a region-specific manner, which may help to identify genes causally related to the development of AngII-induced hypertension. This work was supported by the National Science Centre grant (decision no. DEC-2012/07/D/NZ4/00644).
2017-02-20 | GSE75815 | GEO
Project description:Hypothalamic tanycytes as mediators of maternally programmed seasonal plasticity
| PRJNA842667 | ENA
Project description:RhoBTB1 Reverses Established Arterial Stiffness in Angiotensin II Hypertension
| PRJNA781123 | ENA
Project description:Oxidative injury and inflammation have been implicated in the genesis of hypertension but the mechanisms involved are not fully understood. We describe a new pathway in which angiotensin II promotes dendritic cell (DC) activation of T cells and ultimately hypertension. NADPH oxidase-dependent superoxide production is increased 5-fold in DCs isolated from hypertensive mice as compared to sham-treated mice. This is associated with DC accumulation of protein-isoketal adducts and production of IL-6, IL-1β and IL-23. DCs from hypertensive mice but not sham mice promote survival and proliferation of CD8+ T cells in culture. Chemically diverse isoketal scavengers not only prevent activation and immunogenicity of DCs, but also attenuate angiotensin II-induced hypertension. Moreover, adaptive transfer of DCs from hypertensive mice prime development of hypertension in response to a subpressor dose of angiotensin II. Exposure of DCs to tert butyl hypdroperoxide promoted isoketal formation, DC stimulation of CD8+ T cell proliferation and primed hypertension in response to low dose angiotensin II. Serum isoprostanes, precursors to isoketals, were found to be elevated in humans with treated hypertension and were markedly elevated in patients with resistant hypertension. These studies show that angiotensin II-induced hypertension activates DCs, in large part by causing superoxide production and formation of isoketals. They define a new mechanism of hypertension and identify a potential new therapeutic approach for this disease. We used microarrays to detail the expression differences in dendritic cells under hypertensive conditions. Dendritic cells were isolated from mosue spleen and subsequently treated with Angiotensin II with or without co-treatment with 2-hydroxybenzylamine (2-HOBA) for RNA extraction and hybridization on Affymetrix microarrays. We sought to determine the effect of oxidative stress on dendritic cell expression profiles.
2014-07-16 | E-GEOD-59422 | biostudies-arrayexpress
Project description:High maternal estradiol is reported to induce metabolic disorders by modulating hypothalamic gene expression in offspring. Since neurogenesis plays a crucial role during hypothalamus development, we explored whether prenatal high estradiol exposure (HE) affects proliferation and differentiation of fetal hypothalamic neural stem/progenitor cells (NSC/NPCs) in mice and performed RNA sequencing to identify the critical genes involved. NSC/NPCs in HE mice presented attenuated cell proliferation but increased neuronal differentiation in vitro compared with control (NC) cells. Gene set enrichment analysis of mRNA profiles indicated that genes downregulated in HE NSC/NPCs were enriched in neurogenesis-related Gene Ontology (GO) terms, while genes upregulated in HE NSC/NPCs were enriched in response to estradiol. Protein-protein interaction analysis of genes with core enrichment in GO terms of neurogenesis and response to estradiol identified 10 Hub mRNAs, among which three were potentially correlated with six differentially expressed (DE) lncRNAs based on lncRNA profiling and co-expression analysis. These findings offer important insights into developmental modifications in hypothalamic NSC/NPCs and may provide new clues for further investigation on maternal environment programmed neural development disorders.
2021-06-01 | GSE168075 | GEO