Short Leukocyte Telomere Length Precedes Clinical Expression of Atherosclerosis: The Blood-and-Muscle Model.
Short Leukocyte Telomere Length Precedes Clinical Expression of Atherosclerosis: The Blood-and-Muscle Model.
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DOI：
10.1161/circresaha.117.311751
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发表时间：
2018-02-16
影响因子：
20.1
通讯作者：
Aviv A
中科院分区：
文献类型：
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作者：
Benetos A;Toupance S;Gautier S;Labat C;Kimura M;Rossi PM;Settembre N;Hubert J;Frimat L;Bertrand B;Boufi M;Flecher X;Sadoul N;Eschwege P;Kessler M;Tzanetakou IP;Doulamis IP;Konstantopoulos P;Tzani A;Korou M;Gkogkos A;Perreas K;Menenakos E;Samanidis G;Vasiloglou-Gkanis M;Kark JD;Malikov S;Verhulst S;Aviv A
补充数字内容可在文本中找到。白细胞端粒长度短与动脉粥样硬化性心血管疾病（ASCVD）相关。目前尚不清楚这种关系是否源于出生时固有的短白细胞TL（LTL）或出生后更快的LTL损耗。LTL代表高度增殖的造血系统中的TL，而骨骼肌中的TL代表最低限度复制的组织。我们测量了同一个体的LTL和肌肉TL（MTL），以期获得终身LTL磨损的比较指标，并了解LTL与ASCVD的时间关联。我们的发现队列包括259名年龄为63±14岁（平均值±SD）的个体，接受手术，有（n=131）或无（n=128）ASCVD临床表现。在所有受试者中，经肌肉活检部位调整的MTL（MTLA）长于LTL，ASCVD患者和对照组的LTL-MTLA差距同样随着年龄的增长而扩大。年龄和性别校正的LTL（P=0.005），但不是MTLA（P=0.90），ASCVD患者比对照组短。ASCVD患者白细胞与肌肉之间的TL间隙（LTL-MTLA）较对照组宽（P=0.0003），白细胞与肌肉之间的TL比值（LTL/MTLA）较对照组小（P=0.0001）。研究结果在一个由143名个体组成的队列中重复。这是第一项应用血液和肌肉TL模型的研究，显示ASCVD患者的LTL损耗比对照组更明显。LTL损耗的差异与成年期的年龄无关，这表明早期生命的损耗增加更可能是ASCVD患者LTL较短的主要解释。URL：http://www.clinicaltrials.gov。唯一标识符：NCT 02176941。
Supplemental Digital Content is available in the text. Short telomere length (TL) in leukocytes is associated with atherosclerotic cardiovascular disease (ASCVD). It is unknown whether this relationship stems from having inherently short leukocyte TL (LTL) at birth or a faster LTL attrition thereafter. LTL represents TL in the highly proliferative hematopoietic system, whereas TL in skeletal muscle represents a minimally replicative tissue. We measured LTL and muscle TL (MTL) in the same individuals with a view to obtain comparative metrics for lifelong LTL attrition and learn about the temporal association of LTL with ASCVD. Our Discovery Cohort comprised 259 individuals aged 63±14 years (mean±SD), undergoing surgery with (n=131) or without (n=128) clinical manifestation of ASCVD. In all subjects, MTL adjusted for muscle biopsy site (MTLA) was longer than LTL and the LTL-MTLA gap similarly widened with age in ASCVD patients and controls. Age- and sex-adjusted LTL (P=0.005), but not MTLA (P=0.90), was shorter in patients with ASCVD than controls. The TL gap between leukocytes and muscle (LTL-MTLA) was wider (P=0.0003), and the TL ratio between leukocytes and muscle (LTL/MTLA) was smaller (P=0.0001) in ASCVD than in controls. Findings were replicated in a cohort comprising 143 individuals. This first study to apply the blood-and-muscle TL model shows more pronounced LTL attrition in ASCVD patients than controls. The difference in LTL attrition was not associated with age during adulthood suggesting that increased attrition in early life is more likely to be a major explanation of the shorter LTL in ASCVD patients. URL: http://www.clinicaltrials.gov. Unique identifier: NCT02176941.