Original Article
Copyright ©2014 Baishideng Publishing Group Inc.
World J Cardiol. May 26, 2014; 6(5): 327-337
Published online May 26, 2014. doi: 10.4330/wjc.v6.i5.327
Table 3 DNA methylation and histone modification associated with essential hypertension
Ref.StudySubjectsResultsSite of modification and type
Smolarek et al[68]Humans5-mC significantly higher in healthy subjects than entire group of patients with EHN/A
Wang et al[69]HumansIncreased methylation levels observed at 2-CpG sites in comparison with normotensive controlsSULF1: Methylation
Liang et al[70]HumansRegulation of renal sodium reabsorption β-2 adrenergic stimulation → inhibition of histone deacetylase-8 in kidney → increased histone acetylation and decreased genetic transcription of WNK4 caused increased blood pressure 11β-hydroxysteroid dehydrogenase type 2–converts active glucocorticoids to inactive glucocorticoids Promoter methylation of HSD11B2 gene decreased expression of renal 11β-hydroxysteroid dehydrogenase type 2 affects regulation of volume and BP homeostasis ENaCα-epithelial sodium channel–affects Na+ reabsorption in the distal nephron Proposed mechanism: Methylation of Lys79 of histone H3 suppresses ENaCα transcription ACE1-Angiotensin-converting enzyme ACE1-up-regulated in association with increased binding of histone 3 acetylation (H3Ac) and 4th lysine trimethylation (H3K4me3) and in association with decreased binding of histone ninth lysine residue demethylation (H3K9me2)WNK4: Decreased transcription and increased histone acetylation HSD11B2: Promoter methylation ENaCα: Methylation of Lys79 of histone H3 H3K4me3: Histone 3 acetylation and 4th lysine trimethylation. H3K9me2: Decreased binding of histone 9th lysine residue demethylation
Udali et al[71]Friso et al[72]Humans11β-hydroxysteroid dehydrogenase 2 methylation at HSD11B2 promoter in DNA of PBMCs of hypertensive patients inversely related to enzyme function Promoter methylation of HSD11B2 gene plays a role in HTNHSD11B2: Methylation in promoter region
Lee et al[73]RatsNa+-K+-2 Cl- cotransporter 1 (NKCC1) Methylation status of NKCC1 promoter–elevated in hearts of spontaneously hypertensive rats SHRs–significant hypomethylation of NKCC1 associated with increase in gene expression contributing to HTNNKCC1: Methylation in promoter region NKCC1: Hypomethylation in promoter region
Riviere et al[74]Human endothelial cell lines and rats in vivoSomatic angiotensin-converting enzyme (= ACE1) Promoter methylation levels: Higher levels of methylation associated with transcriptional repression Therefore hypomethylation of promoter region of sACE could contribute to HTNsACE: Methylation in promoter region
Millis[75]HumanMethyl CpG binding protein-2 (MECP-2) Methylates and thereby silences the expression of the norepinephrine transporter gene Phenyl-ethanolamine N-methyltransferase (PMNT)–converts Norepinephrine into Epinephrine Also mimics gene-silencing actions of MECP-2 Leads to increased synaptic levels of catecholamines (increased Epinephrine release and decreased Norepinephrine reuptake) CTGF Lysine methyltransferase that methylates the histone H3K79 site of nucleosomes that inhibits the expression of CTGF (in the cells of the collecting ducts)MECP-2: Methylation PMNT: Methylation H3K79: Methylation of histone site of nucleosomes