Fetal programming and epigenetic mechanisms in arterial hypertension

Abstract

a,Ã Purpose of reviewTo provide an overview of available evidence of the potential role of epigenetics in the pathogenesis of hypertension and vascular dysfunction. Recent findingsArterial hypertension is a highly heritable condition. Surprisingly, however, genetic variants only explain a tiny fraction of the phenotypic variation and the term 'missing heritability' has been coined to describe this phenomenon. Recent evidence suggests that phenotypic alteration that is unrelated to changes in DNA sequence (thereby escaping detection by classic genetic methodology) offers a potential explanation. Here, we present some basic information on epigenetics and review recent work consistent with the hypothesis of epigenetically induced arterial hypertension. SummaryNew technologies that enable the rigorous assessment of epigenetic changes and their phenotypic consequences may provide the basis for explaining the missing heritability of arterial hypertension and offer new possibilities for treatment and/or prevention.

Epigenetics of Arterial Hypertension

“…-АГ [1,13]. Навколишнє середовище впливає на серцево-судинну систему, може викликати такі патологічні стани, як атеросклероз або інфаркт міокарда [14].…”

“…За останні 20 років проведена велика кількість досліджень з вивчення ролі поліморфізмів різних генів-кандидатів у ґенезі захворюван-ня. Однак фенотипічні особливості часто не пов'язані зі змінами послідовності ДНК [1].…”

Feto-maternal interactions

“…In line with this concept, vulnerable periods during early life known to be associated with fetal programming of cardiovascular disease coincide with increased epigenetic activity. The review article by Scherrer et al [8] highlights the potential contribution of fetal programming to the pathogenesis of arterial hypertension: studies in young offspring of mothers suffering from preeclampsia [9] and in apparently healthy children conceived by assisted reproductive technologies (ART) [10,11] have shown that these children display premature vascular aging and increased BP. Studies in animal models of these two entities have shown that epigenetic dysregulation with consequent altered expression of genes important for BP regulation [that is, endothelial nitric oxide synthase (eNOS)] plays a central role in the pathogenesis of arterial hypertension [12,13].…”

Hydrogen sulfide alleviates hypertensive kidney dysfunction through an epigenetic mechanism

“…In recent years, a considerable number of studies have sought to investigate the epigenetic mechanisms of gene regulation in renal development and function and hypertension (15,20,37,50,53). Epigenetics is defined as the study of the molecular mechanisms that regulate gene expression often leading to reversible changes that can be stable throughout the lifespan of an organism and potentially be heritable (11,40,49). DNA hypermethylation of the RASAL1 gene and dysregulation of miR-132, miR-212, miR-181b, and miR-663 in the RAS are two epigenetic mechanisms that have been studied in the context of hypertension in the kidney (3,4,6,10,28).…”