This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: 100/4/520    most recent 01.RES.0000258855.60637.58v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bogdarina, I. Articles by Clark, A. J.L. Search for Related Content PubMed PubMed Citation Articles by Bogdarina, I. Articles by Clark, A. J.L. Related Collections Nutrition ACE/Angiotension receptors Animal models of human disease Gene expression Hypertension - basic studies Related Article

(Circulation Research. 2007;100:520.)
© 2007 American Heart Association, Inc.

Molecular Medicine

Epigenetic Modification of the Renin-Angiotensin System in the Fetal Programming of Hypertension

Irina Bogdarina, Simon Welham, Peter J. King, Shamus P. Burns, Adrian J.L. Clark

From the Centre for Endocrinology (I.B., S.W., P.J.K., A.J.L.C.), Barts & the London, Queen Mary University of London, UK; Department of Chemical and Biological Sciences (S.P.B.), University of Huddersfield, UK.

Correspondence to Professor A.J.L. Clark, Centre for Endocrinology, John Vane Science Centre, William Harvey Research Institute, Charterhouse Square, London EC1M 6BQ, UK. E-mail a.j.clark{at}qmul.ac.uk

Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Lifelong environmental factors (eg, salt intake, obesity, alcohol) and genetic factors clearly contribute to the development of hypertension, but it has also been established that stress in utero may program the later development of the disease. This phenomenon, known as fetal programming can be modeled in a range of experimental animal models. In maternal low protein diet rat models of programming, administration of angiotensin converting enzyme inhibitors or angiotensin receptor antagonists in early life can prevent development of hypertension, thus implicating the renin-angiotensin system in this process. Here we show that in this model, expression of the AT_1b angiotensin receptor gene in the adrenal gland is upregulated by the first week of life resulting in increased receptor protein expression consistent with the increased adrenal angiotensin responsiveness observed by others. Furthermore, we show that the proximal promoter of the AT_1b gene in the adrenal is significantly undermethylated, and that in vitro, AT_1b gene expression is highly dependent on promoter methylation. These data suggest a link between fetal insults to epigenetic modification of genes and the resultant alteration of gene expression in adult life leading ultimately to the development of hypertension. It seems highly probable that similar influences may be involved in the development of human hypertension.

Key Words: hypertension • angiotensin receptors • fetal programming • DNA methylation

Related Article:

Developmental Programming Through Epigenetic Changes

Anne Monique Nuyt and Moshe Szyf
Circ. Res. 2007 100: 452-455. [Full Text] [PDF]

This article has been cited by other articles:

				P. D. Gluckman, M. A. Hanson, C. Cooper, and K. L. Thornburg Effect of In Utero and Early-Life Conditions on Adult Health and Disease N. Engl. J. Med., July 3, 2008; 359(1): 61 - 73. [Full Text] [PDF]

				P. Stenvinkel and T. J. Ekstrom Epigenetics--a helpful tool to better understand processes in clinical nephrology? Nephrol. Dial. Transplant., May 1, 2008; 23(5): 1493 - 1496. [Full Text] [PDF]

				A. C. Aragon, P. G. Kopf, M. J. Campen, J. K. Huwe, and M. K. Walker In Utero and Lactational 2,3,7,8-Tetrachlorodibenzo-p-dioxin Exposure: Effects on Fetal and Adult Cardiac Gene Expression and Adult Cardiac and Renal Morphology Toxicol. Sci., February 1, 2008; 101(2): 321 - 330. [Abstract] [Full Text] [PDF]

				A. M. Nuyt and M. Szyf Developmental Programming Through Epigenetic Changes Circ. Res., March 2, 2007; 100(4): 452 - 455. [Full Text] [PDF]