Association between oxidative DNA damage and telomere shortening in circulating endothelial progenitor cells obtained from metabolic syndrome patients with coronary artery disease
Association between oxidative DNA damage and telomere shortening in circulating endothelial progenitor cells obtained from metabolic syndrome patients with coronary artery disease
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DOI：
10.1016/j.atherosclerosis.2007.09.040
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发表时间：
2008-06-01
期刊：
影响因子：
5.3
通讯作者：
Nakamura, Motoyuki
中科院分区：
文献类型：
--
作者：
Satoh, Mamoru;Ishikawa, Yuh;Nakamura, Motoyuki
代谢综合征（MS）诱导氧化应激增加，可能是冠状动脉疾病（CAD）的重要促成因素。内皮祖细胞端粒缩短可能是内皮细胞衰老的关键因素。端粒缩短的速率高度依赖于细胞氧化损伤。本研究分析了合并MS和不合并MS的CAD患者的EPCs端粒缩短与DNA氧化损伤的关系。我们分析了57例CAD患者（急性心肌梗死[AMI]， n = 26；稳定型心绞痛[AP]， n = 31）和21例年龄匹配的健康受试者（对照组）外周血循环EPCs。冠心病患者的端粒长度和端粒酶活性明显低于对照组，AMI患者的端粒长度和端粒酶活性明显低于AP患者。CAD患者的DNA氧化损伤高于对照组，AMI患者的DNA氧化损伤也高于AP患者。端粒长度与DNA氧化损伤呈负相关。CAD合并MS患者的端粒长度和端粒酶活性低于未合并MS的患者，CAD合并MS患者的DNA氧化损伤高于未合并MS的患者。在我们的体外研究中，氧化处理导致端粒缩短和EPCs端粒酶活性降低。这些结果表明，通过DNA氧化损伤增加的EPC端粒缩短可能在CAD的发病机制中起重要作用。此外，MS可能与DNA氧化损伤增加和EPC端粒缩短有关。2007爱思唯尔爱尔兰有限公司版权所有。
Metabolic syndrome (MS) induces an increase in oxidative stress and may be an important contributory factor for coronary artery disease (CAD). Telomere shortening of endothelial progenitor cells (EPCs) may be the key factor in endothelial cell senescence. The rate of telomere shortening is highly dependent on cellular oxidative damage. This study analyzed the relationship between telomere shortening and oxidative DNA damage in EPCs obtained from CAD patients with MS and without MS. We analyzed circulating EPCs in peripheral blood obtained from 57 patients with CAD (acute myocardial infarction [AMI], n = 26; stable angina pectoris [AP], n = 31) and 21 age-matched healthy subjects (control). Telomere length and telomerase activity were significantly lower in CAD patients than in controls, and were lower in AMI patients than in AP patients. Oxidative DNA damage was higher in CAD patients compared with controls, and oxidative DNA damage in AMI patients was also higher than in AP patients. There was a negative correlation between telomere length and oxidative DNA damage. Telomere length and telomerase activity were lower in CAD patients with MS than in those without MS. Oxidative DNA damage in CAD patients with MS was higher than in those without MS. In our in vitro study, oxidative treatments induced telomere shortening and decrease in telomerase activity of EPCs. These results suggest that EPC telomere shortening via increased oxidative DNA damage may play an important role in the pathogenesis of CAD. In addition, MS may be related to increased oxidative DNA damage and EPC telomere shortening. (C) 2007 Elsevier Ireland Ltd. All rights reserved.