Degenerative aortic valve stenosis, but not coronary disease, is associated with shorter telomere length in the elderly
Degenerative aortic valve stenosis, but not coronary disease, is associated with shorter telomere length in the elderly
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DOI：
10.1161/01.atv.0000222961.24912.69
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发表时间：
2006-06-01
影响因子：
8.7
通讯作者：
Lüscher, TF
中科院分区：
文献类型：
--
作者：
Kurz, DJ;Kloeckener-Gruissem, B;Lüscher, TF
目的：钙化性主动脉瓣狭窄（CAS）发病率与年龄相关性增加的机制尚不清楚，但可能包括端粒驱动的细胞衰老。由于端粒长度在相同年龄的个体之间差异很大，我们假设端粒较短的患者在生命的后期更容易发展为CAS。方法和结果-平均端粒长度在193例年龄>= 70岁的CAS和不CAS患者的白细胞中测量。在年龄、性别、有无冠心病配对的30名CAS患者和对照组中进行的初步实验表明，CAS组的端粒明显较短，Southern印迹杂交显示，（5.75 +/- 0.55 kbp对6.27 +/- 0.7 kbp，P = 0.0023）和基于定量聚合酶链反应的技术（相对端粒长度0.88 +/- 0.19对1.0 +/- 0.19，P = 0.01）。然后在整个队列中证实了这一发现（CAS n = 64，对照n = 129，相对端粒长度= 0.86 +/- 0.16 vs 0.94 +/- 0.12，P = 0.0003）。两组的潜在混杂特征相当。根据冠状动脉疾病的存在或不存在的亚组分析表明，这种疾病与端粒长度没有关联。结论-在老年人中，钙化性主动脉瓣狭窄，而不是冠状动脉疾病，与较短的白细胞端粒长度。
Objective - The mechanisms responsible for the age-related increase in the incidence of calcific aortic valve stenosis (CAS) are unclear but may include telomere-driven cellular senescence. Because telomere length varies widely among individuals of the same age, we hypothesized that patients with shorter telomeres would be prone to develop CAS late in life.Methods and Results - Mean telomere length was measured in leukocytes from a cohort of 193 patients >= 70 years of age with and without CAS. Pilot experiments performed in 30 patients with CAS and controls pair- matched for age, sex, and presence or absence of coronary disease demonstrated significantly shorter telomeres in the CAS group both by Southern blot hybridization (5.75 +/- 0.55 kbp versus 6.27 +/- 0.7 kbp, P = 0.0023) and by a quantitative polymerase chain reaction-based technique (relative telomere length 0.88 +/- 0.19 versus 1.0 +/- 0.19, P = 0.01). This finding was then confirmed in the whole cohort (CAS n = 64, controls n = 129, relative telomere length = 0.86 +/- 0.16 versus 0.94 +/- 0.12, P = 0.0003). Both groups were comparable for potential confounding characteristics. Subgroup analysis according to the presence or absence of coronary disease demonstrated no association of this disorder with telomere length.Conclusions - In the elderly, calcific aortic stenosis, but not coronary disease, is associated with shorter leukocyte telomere length.