{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:12:57Z","timestamp":1787008377857,"version":"build-2736575974"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,8,12]],"date-time":"2025-08-12T00:00:00Z","timestamp":1754956800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000050","name":"NHLBI","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 HL 122742"],"award-info":[{"award-number":["RO1 HL 122742"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 HL 130344"],"award-info":[{"award-number":["RO1 HL 130344"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 HL 146628"],"award-info":[{"award-number":["RO1 HL 146628"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009230","name":"Norris Cotton Cancer Center","doi-asserted-by":"publisher","award":["P30CA023108"],"award-info":[{"award-number":["P30CA023108"]}],"id":[{"id":"10.13039\/100009230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Hypertension is caused by a combination of genetic and environmental factors. Angiotensinogen (AGT) is a component of renin-angiotensin-aldosterone system, which regulates blood pressure. Genome-wide association studies have shown that two A\/G polymorphisms (rs2493134 and rs2004776), located at +507 and +1164 in intron I of the human AGT (hAGT) gene, are linked to hypertension. AGT polymorphisms result in two haplotypes, Hap-I a pro-hypertensive, whereas Hap-II is normotensive. Previous studies support the role of epigenetics in blood pressure regulation. In this study, we generated transgenic mice (TG) with hAGT containing Hap-I and Hap-II variants to investigate the effect of high salt diet (HSD) on epigenetics and transcriptional regulation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We treated Hap-I and Hap-II TG mice with 4% HSD and identified DNA methylation patterns. We measured hAGT mRNA and protein by qPCR and immunoblot, respectively. Chromatin immunoprecipitation assay and RNA sequencing were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>hAGT gene expression is increased by HSD in both Hap-I and Hap-II TG mice. In the liver and kidney, we observed significantly higher DNA demethylation (less CpG\u2019s) and stronger binding of transcription factors in the promoter of Hap-I TG mice as compared to Hap-II post HSD. RNA-Seq identified differentially expressed genes, novel target genes, canonical pathways, and upstream regulators associated with hypertension.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Our findings identified a novel high salt-sensitive risk haplotype, novel CpG sites and DNA methylation patterns, potential gene targets, and pathways implicated in hypertension. Combining epigenetic and transcriptional analysis allows for a more holistic understanding of the regulatory mechanisms that govern the hAGT gene.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ajh\/hpaf150","type":"journal-article","created":{"date-parts":[[2025,8,8]],"date-time":"2025-08-08T12:10:24Z","timestamp":1754655024000},"page":"74-87","source":"Crossref","is-referenced-by-count":4,"title":["Effect of Dietary Salt Excess on DNA Methylation and Transcriptional Regulation of Human Angiotensinogen Gene\u00a0Expression"],"prefix":"10.1093","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4925-6720","authenticated-orcid":false,"given":"Sravan","family":"Perla","sequence":"first","affiliation":[{"name":"Department of Pathology, New York Medical College , Valhalla, New York ,","place":["USA"]},{"name":"Department of Physiology and Pharmacology, University of Toledo College of Medicine and Life Sciences , Toledo, Ohio ,","place":["USA"]},{"name":"Department 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