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

Research output: Contribution to journalArticle

336 Citations (Scopus)

Abstract

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 AT1b 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 AT1b gene in the adrenal is significantly undermethylated, and that in vitro, AT1b 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.
Original languageEnglish
Pages (from-to)520-526
Number of pages7
JournalCirculation Research
Volume100
Issue number4
Early online date1 Mar 2007
DOIs
Publication statusPublished - 2 Mar 2007

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Renin-Angiotensin System
Fetal Development
Epigenomics
Hypertension
Genes
Gene Expression
Cerebrovascular Disorders
Protein-Restricted Diet
Angiotensin Type 1 Receptor
Angiotensin Receptor Antagonists
Angiotensins
Human Development
Adrenal Glands
Angiotensin-Converting Enzyme Inhibitors
Methylation
Cardiovascular Diseases
Animal Models
Obesity
Salts
Alcohols

Cite this

Bogdarina, Irina ; Welham, Simon ; King, Peter J. ; Burns, Shamus P. ; Clark, Adrian J.L. / Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. In: Circulation Research. 2007 ; Vol. 100, No. 4. pp. 520-526.
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Epigenetic modification of the renin-angiotensin system in the fetal programming of hypertension. / Bogdarina, Irina; Welham, Simon; King, Peter J.; Burns, Shamus P.; Clark, Adrian J.L.

In: Circulation Research, Vol. 100, No. 4, 02.03.2007, p. 520-526.

Research output: Contribution to journalArticle

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