SCOPE: We previously demonstrated that protein restriction in utero induced salt-sensitive hypertension and changed renal levels of angiotensin type 2 receptor (AT2R) in Stroke-Prone Spontaneously Hypertensive Rat (SHRSP). Here, we investigated if this characteristic alteration of AT2R is related to AT2R DNA methylation profiles. METHODS AND RESULTS: First, we examined the relation between AT2R DNA methylation and its promoter activity in vitro. Luciferase assays revealed a negative correlation between these two variables. Next, we fed SHRSP dams and grand-dams a control 20% casein diet or a 9% casein diet during pregnancy. Adult offspring and grand-offspring were supplied either water or 1% saline solution for 2 weeks. Renal AT2R promoter DNA near the TATA-box was hypomethylated, mRNA expression was suppressed, and protein expression tended to be higher, in adult offspring of mothers fed a low casein diet. Moreover, adult grand-offspring exhibited high blood pressure after salt loading, along with suppressed transcription of AT2R mRNA and elevated translated protein. CONCLUSIONS: Under a fetal environment of protein restriction, the increase in protein expression due to hypomethylation of the AT2R promoter region occurs as a response to increased salt sensitivity, and controlling this mechanism may be important for the prevention of hypertension.
SCOPE: We previously demonstrated that protein restriction in utero induced salt-sensitive hypertension and changed renal levels of angiotensin type 2 receptor (AT2R) in Stroke-Prone Spontaneously Hypertensive Rat (SHRSP). Here, we investigated if this characteristic alteration of AT2R is related to AT2R DNA methylation profiles. METHODS AND RESULTS: First, we examined the relation between AT2R DNA methylation and its promoter activity in vitro. Luciferase assays revealed a negative correlation between these two variables. Next, we fed SHRSP dams and grand-dams a control 20% casein diet or a 9% casein diet during pregnancy. Adult offspring and grand-offspring were supplied either water or 1% saline solution for 2 weeks. Renal AT2R promoter DNA near the TATA-box was hypomethylated, mRNA expression was suppressed, and protein expression tended to be higher, in adult offspring of mothers fed a low casein diet. Moreover, adult grand-offspring exhibited high blood pressure after salt loading, along with suppressed transcription of AT2R mRNA and elevated translated protein. CONCLUSIONS: Under a fetal environment of protein restriction, the increase in protein expression due to hypomethylation of the AT2R promoter region occurs as a response to increased salt sensitivity, and controlling this mechanism may be important for the prevention of hypertension.
Authors: Lucinda M Hilliard; Charis L E Chow; Katrina M Mirabito; U Muscha Steckelings; Thomas Unger; Robert E Widdop; Kate M Denton Journal: Hypertension Date: 2014-05-19 Impact factor: 10.190
Authors: Vu Thao-Vi Dao; Sawsan Medini; Marion Bisha; Vera Balz; Tatsiana Suvorava; Murat Bas; Georg Kojda Journal: Biochem Pharmacol Date: 2016-05-26 Impact factor: 5.858