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Telomeres, atherosclerosis, and the hemothelium: the longer view.
Annual Review of Medicine ( IF 10.5 ) Pub Date : 2011-10-17 , DOI: 10.1146/annurev-med-050311-104846
Abraham Aviv 1 , Daniel Levy
Affiliation  

The model we propose to explain the links between atherosclerosis and telomere dynamics (birth telomere length and its age-dependent shortening) in leukocytes takes cues from three facts: atherosclerosis is a disease of the vascular endothelium; the hematopoietic system and the vascular endothelium share a common embryonic origin; interindividual variation in leukocyte telomere length (LTL) in the general population has a genetic explanation. The model posits that LTL dynamics mirror telomere dynamics in hematopoietic stem cells (HSCs), where telomere length is an index of HSC reserves. Diminished HSC reserves at birth, their accelerated attrition rate afterward, or both are are reflected in shortened LTL during adulthood-a phenomenon that confers increased risk for atherosclerosis. We explain how telomere length in HSCs serves as both a biomarker of atherosclerosis and a determinant of its development. Our model comes down to this proposition: Shortened LTL predicts increased atherosclerotic risk because the injurious component of atherosclerosis exceeds the repair capacity of HSC reserves, which largely depend on HSC telomere length.

中文翻译:

端粒、动脉粥样硬化和血皮:更长远的观点。

我们提出的用于解释白细胞中动脉粥样硬化和端粒动力学(出生端粒长度及其与年龄相关的缩短)之间联系的模型从三个事实中获得线索:动脉粥样硬化是一种血管内皮疾病;造血系统和血管内皮共享一个共同的胚胎起源;一般人群中白细胞端粒长度 (LTL) 的个体差异具有遗传解释。该模型假定 LTL 动力学反映了造血干细胞 (HSC) 中的端粒动力学,其中端粒长度是 HSC 储备的指标。出生时 HSC 储备减少、之后加速的损耗率或两者都反映在成年期 LTL 缩短 - 这种现象会增加动脉粥样硬化的风险。我们解释了 HSC 中的端粒长度如何既作为动脉粥样硬化的生物标志物又是其发展的决定因素。我们的模型归结为这个命题:缩短的 LTL 预测动脉粥样硬化风险增加,因为动脉粥样硬化的有害成分超过了 HSC 储备的修复能力,这在很大程度上取决于 HSC 端粒长度。
更新日期:2012-01-16
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