期刊
ATHEROSCLEROSIS
卷 231, 期 1, 页码 173-179出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2013.08.029
关键词
Leukocyte; Telomere length; Homocysteine; DNA methyaltion; hTERT; Atherosclerosis
资金
- National Natural Science Foundation of China [81200224]
- Medical Science Research Foundation of Guangdong Province in China [2012B2012248]
- PUMC Youth Fund
- Fundamental Research Funds for the Central Universities [3332013004]
Aims: Leukocyte telomere length (LTL) is shortened in patients with clinical atherosclerosis (AS). Here we aimed to explore the contribution of elevated homocysteine (Hcy) level to LTL shortening in AS patients and the underlying mechanism. Methods: Circulating leukocytes were collected from 197 patients with AS and 165 sex-and age-matched healthy subjects for LTL determination. mRNA expression or DNA methylation of human telomerase reverse transcriptase (hTERT) was determined by real-time PCR and methylation-specific PCR assay, respectively. We established a hyperhomocysteinemia (HHcy) mice model to confirm human results. Results: Hcy was negatively correlated with LTL shortening in AS patients (r = -0.179, p = 0.015) and controls (r = -0.146, p = 0.031). Serum folate and high-sensitivity C-reactive protein levels significantly interacted with Hcy in LTL shortening. Hcy was related to hTERT mRNA downregulation and promoter demethylation, which combined was associated with LTL shortening in AS patients. Hcy-induced LTL shortening did not differ by sites of AS lesions or infarction. Similar to clinical observations, our HHcy mice model suggested that Hcy induced DNA demethylation and downregulation of mouse TERT and further contributed to LTL shortening. Conclusions: Elevated Hcy level induced DNA demethylation of hTERT and was closely related with hTERT downregulation, which led to LTL shortening in AS. These findings provide novel insights into an epigenetic mechanism for Hcy-related AS. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据