Telomere shortening in human coronary artery diseases
Telomere shortening in human coronary artery diseases
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DOI：
10.1161/01.atv.0000117200.46938.e7
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发表时间：
2004-03-01
影响因子：
8.7
通讯作者：
Ueda, M
中科院分区：
文献类型：
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作者：
Ogami, M;Ikura, Y;Ueda, M
背景-损伤后细胞更新增加被认为在动脉粥样硬化斑块的发展中起重要作用。端粒缩短已被证明与细胞更新有关。我们评估了端粒长度的人冠状动脉内皮细胞，以澄清是否有端粒缩短和冠状动脉disease（CAD）之间的关系。方法和结果-冠状动脉内皮细胞从11例CAD谁进行尸检和22例无CAD谁进行尸检刮离冠状动脉的管腔表面。从内皮细胞提取的DNA印迹并与端粒特异性寡核苷酸（[ TTAGGG] 4）杂交。用着丝粒DNA含量（T/C比）标准化代表端粒DNA含量的杂交信号强度，以估计端粒长度。冠心病患者的T/C比值显著小于年龄匹配的非冠心病患者（冠心病患者，0.462 ± 0.135;非冠心病患者，1.002 ± 0.212）（P < 0.0001）。在6个单独的CAD患者中，在动脉粥样硬化病变的T/C比显着小于（P < 0.05）在非动脉粥样硬化portion.Conclusions -这些研究结果表明，局部复制衰老和端粒缩短的内皮细胞可能在冠状动脉粥样硬化和CAD中发挥关键作用。
Background - Increased cell turnover in response to injury is considered to be important in the development of atherosclerotic plaques. Telomere shortening has been shown to be associated with cell turnover. We assessed the telomere length of human coronary endothelial cells to clarify whether there is a relationship between telomere shortening and coronary artery disease (CAD).Methods and Results - Coronary endothelial cells were obtained from 11 patients with CAD who underwent autopsy and 22 patients without CAD who underwent autopsy by scraping off the luminal surface of coronary arteries. DNA extracted from the endothelial cells were blotted and hybridized with telomere-specific oligonucleotide ([ TTAGGG] 4). The hybridization signal intensity, which represented telomeric DNA content, was standardized with centromeric DNA content (T/C ratio) to estimate telomere length. The T/C ratios were significantly smaller ( P < 0.0001) in CAD patients than in age-matched non-CAD patients ( CAD patients, 0.462 +/- 0.135; non-CAD patients, 1.002 +/- 0.212). In 6 individual CAD patients, the T/C ratio at the atherosclerotic lesion was significantly smaller ( P < 0.05) than that at the non-atherosclerotic portion.Conclusions - These findings suggest that focal replicative senescence and telomere shortening of endothelial cells may play a critical role in coronary atherogenesis and CAD.