DNA Methylation of Human Telomerase Reverse Transcriptase Associated With Leukocyte Telomere Length Shortening in Hyperhomocysteinemia-Type Hypertension in Humans and in a Rat Model

Abstract

Circulation Journal Official Journal of the Japanese Circulation Society http://www. j-circ.or.jp aging-related diseases. Particularly, clinical epidemiological studies and studies of telomerase-deficient mice have shown a direct link between telomere shortening and hypertension. 6 In addition, experimental evidence reveals that both elevated Hcy level and hypertension are related to DNA methylation of leukocytes and are associated with the burden of oxidative stress, inflammation, altered elasticity of the vascular wall, and renal function; all key contributors to age-dependent shortening of leukocyte telomere length (LTL). 7 Our previous in vivo and in vitro studies demonstrated that Hcy could promote the recruitment of methylation-sensitive transcription factors to demethylated promoters of atherosclerosis-related genes by reducing DNA methyltransferase 1 activity. 8, 9 The human telomerase reverse transcriptase (hTERT) gene might regulate telomerase activity and maintain telomere length by encoding the catalytic subunit of the telomerase holoenzyme. 5 The hTERT level is tightly regulated by DNA methssential hypertension (EH) is a complex disorder involving approximately one-third of the adult population worldwide. 1,2 Epidemiological studies have documented that aging as well as genetic and environmental factors such as physical inactivity, obesity, high sodium and low potassium diet, and alcohol consumption are associated with the development of hypertension. 3,4 In addition, dysregulated methionine metabolism leading to high plasma homocysteine (Hcy) levels (≥10 mmol/L), known as hyperhomocysteinemia-type EH (HHcy-EH), might play a role. 5 However, the mechanisms underlying HHcy-EH and its adverse complications remain unknown. Editorial p 1828Telomere dynamics (telomere length and its age-dependent shortening) provide valuable insights into the pathogenesis of Background: Elevated homocysteine (Hcy) levels might play a role in the development of essential hypertension (EH). Telomere dynamics provide valuable insight into the pathogenesis of age-related diseases. The contribution of Hcy to leukocyte telomere length (LTL) shortening in EH and the underlying mechanism was examined.

High‐methionine diets accelerate atherosclerosis by HHcy‐mediated FABP4 gene demethylation pathway via DNMT1 in ApoE−/− mice

“…Hcy is an intermediate product of the methionine cycle that affects gene expression by DNA methylation modification [18]. DNA methylation occurs by covalent addition of a methyl group from the methyl donor S-adenosylmethionine (SAM) to the 5 0 carbon of the cytosine ring in CpG pairs.…”

Telomeres and essential hypertension

“…Examination of telomere dynamics provides valuable insight into the pathogenesis of age-related conditions such as hypertension, and facilitates understanding of the mechanisms underlying disease [10]. We have systematically analyzed studies about the clinical and biological relevance of telomeres in essential hypertension.…”

<i>Circulation Journal</i> Awards for the Year 2014

“…Conclusions: Elevated Hcy but not hypertension was related to hTERT DNA hypomethylation and reduced mRNA level, thus contributing to the shortening of LTL hypertension. 4 (Circ J 2014;78: 1915-1923 Awards will be presented to the 4 research groups during the 79th Annual Scientific Meeting of the Japanese Circulation Society, and will also be announced on the Society website. We look forward to receiving manuscripts with high scientific impact for publication in Circulation Journal in 2015.…”