Epigenomics of hypertension

Abstract

Multiple genes and pathways are involved in the pathogenesis of hypertension. Epigenomic studies of hypertension are beginning to emerge and hold great promise of providing novel insights into the mechanisms underlying hypertension. Epigenetic marks or mediators including DNA methylation, histone modifications, and noncoding RNA can be studied at a genome or near-genome scale using epigenomic approaches. At the single gene level, several studies have identified changes in epigenetic modifications in genes expressed in the kidney that correlate with the development of hypertension. Systematic analysis and integration of epigenetic marks at the genome-wide scale, demonstration of cellular and physiological roles of specific epigenetic modifications, and investigation of inheritance are among the major challenges and opportunities for future epigenomic and epigenetic studies of hypertension.

Keywords: DNA methylation; Epigenetics; blood pressure; histone modification; kidney.

Figure 1. A tree-like paradigm for understanding the gene and pathway network underlying the development of salt-sensitive hypertension

Figure 2. Several genes expressed in the kidney exhibit changes in epigenetic modifications that correlate with hypertension

mC, DNA methylation; Hm, histone methylation; Ha, histone acetylation; ACE1, angiotensin converting enzyme 1; GC, glucocorticoids; HSD, hydroxysteroid dehydrogenase; GR, glucocorticoid receptor; AR, adrenergic receptor; HDAC, histone deacetylase; MR, mineralocorticoid receptor; ENaC, epithelial sodium channel.

Figure 3. Transgenerational inheritance of epigenetic traits

(Left) Exposure to environmental cues occurs during pregnancy in F0. PGCs that give rise to F2 are exposed. (Right) Exposure occurs in F0 prior to pregnancy. Zygotes in F0 forming the embryo that develops to become F1 are exposed in this scenario. But PGCs that give rise to F2 are not exposed. PGC, primordial germ cell.