ArticleJCI insight2018
Aberrant DNA methylation of hypothalamic angiotensin receptor in prenatal programmed hypertension.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Epigenetic effects of endogenous and exogenous glucocorticosteroids during pregnancy on the offspring: a systematic-narrative review.Hormones (Athens, Greece) · 2025Pooled it
- Pathophysiological Mechanisms and Clinical Controversies of Sodium-Induced Hypertension: A Multi-Systemic Perspective.Nutrients · 2026Review
- Age-varying DNA methylation patterns associated with blood pressure in mid-to-late adulthood.Clinical epigenetics · 2026Article
- Age-varying DNA methylation patterns associated with blood pressure across the lifespan.bioRxiv : the preprint server for biology · 2025Article
- Epigenetic mechanisms of salt-sensitive hypertension.Clinical kidney journal · 2025Review
- Early-Life Hydrogen Sulfide Signaling as a Target for Cardiovascular-Kidney-Metabolic Syndrome Reprogramming.Antioxidants (Basel, Switzerland) · 2025Review
- Animal Models for Studying Developmental Origins of Cardiovascular-Kidney-Metabolic Syndrome.Biomedicines · 2025Review
- Diet-Microbiota-Host Interactions in Regulation of Cardiometabolic Homeostasis: Emerging Mechanisms and Therapeutic Potential.Microbiota and host · 2025Article
- Bone Marrow Niche in Cardiometabolic Disease: Mechanisms and Therapeutic Potential.Circulation research · 2025Review
- Aging and sex differences in salt sensitivity of blood pressure.Clinical science (London, England : 1979) · 2025Review
- Epigenetic Regulation of Innate and Adaptive Immune Cells in Salt-Sensitive Hypertension.Circulation research · 2025Review
- The Fetal Environment and the Development of Hypertension-The Epigenetic Modification by Glucocorticoids.International journal of molecular sciences · 2025Review
- Assessment of ability of AlphaMissense to identify variants affecting susceptibility to common disease.European journal of human genetics : EJHG · 2024Article
- Prenatal LPS leads to increases in RAS expression within the PVN and overactivation of sympathetic outflow in offspring rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2024Article
- Epigenetic Regulation of the Renin-Angiotensin-Aldosterone System in Hypertension.International journal of molecular sciences · 2024Review
- Chromatin modifiers in human disease: from functional roles to regulatory mechanisms.Molecular biomedicine · 2024Review
- DNA demethylation in the hypothalamus promotes transcription of Agtr1a and Slc12a2 and hypertension development.The Journal of biological chemistry · 2024Article
- Epigenetics of the blood pressure reactivity to salt: Is the salt sensitive phenotype correctable?BioImpacts : BI · 2023Article
- The molecular mechanisms in prenatal drug exposure-induced fetal programmed adult cardiovascular disease.Frontiers in pharmacology · 2023Review
- The Role of the Paraventricular-Coerulear Network on the Programming of Hypertension by Prenatal Undernutrition.International journal of molecular sciences · 2022Review
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12 authors.
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No grant is acknowledged in the PubMed record.
Abstract
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.
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