Kurz David J, Kloeckener-Gruissem Barbara, Akhmedov Alexander, Eberli Franz R, Bühler Ines, Berger Wolfgang, Bertel Osmund, Lüscher Thomas F
CardioVascular Center, Cardiology, Hospital, University of Zurich, Zurich, Switzerland.
Arterioscler Thromb Vasc Biol. 2006 Jun;26(6):e114-7. doi: 10.1161/01.ATV.0000222961.24912.69. Epub 2006 Apr 20.
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.
Mean telomere length was measured in leukocytes from a cohort of 193 patients > or =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.
In the elderly, calcific aortic stenosis, but not coronary disease, is associated with shorter leukocyte telomere length.
导致钙化性主动脉瓣狭窄（CAS）发病率随年龄增长而增加的机制尚不清楚，但可能包括端粒驱动的细胞衰老。由于同一年龄段个体的端粒长度差异很大，我们推测端粒较短的患者在晚年更容易发生CAS。
测量了193例年龄≥70岁、患有和未患有CAS的患者白细胞中的平均端粒长度。在30例CAS患者和年龄、性别及是否患有冠心病相匹配的对照组中进行的初步实验表明，通过Southern印迹杂交（CAS组为5.75±0.55kbp，对照组为6.27±0.7kbp，P=0.0023）和基于定量聚合酶链反应的技术（相对端粒长度为0.88±0.19，对照组为1.0±0.19，P=0.01），CAS组的端粒明显更短。这一发现随后在整个队列中得到证实（CAS组n=64，对照组n=129，相对端粒长度=0.86±0.16，对照组为0.94±0.12，P=0.0003）。两组在潜在混杂特征方面具有可比性。根据是否患有冠心病进行的亚组分析表明，该疾病与端粒长度无关。
在老年人中，钙化性主动脉瓣狭窄而非冠心病与白细胞端粒长度较短有关。
