Robarts Research Institute, Schulich School of Medicine and Dentistry, Western University, London, Canada.
Robarts Research Institute, Departments of Medicine, Biochemistry, and Medical Biophysics, Schulich School of Medicine and Dentistry, Western University, London, Canada.
Curr Atheroscler Rep. 2023 Mar;25(3):95-103. doi: 10.1007/s11883-023-01082-6. Epub 2023 Jan 23.
The purpose of the study is to explore the evidence linking telomere length with atherosclerotic ischemic disease.
There has been a recent expansion in strategies for measuring telomere length, including analyzing genome sequence data and capitalizing on genomic loci that associate with telomere length. These, together with more established approaches, have been used to generate a more complete picture of telomere length relationships with ischemic disease. Whereas earlier meta-analyses suggested an association between short leukocyte telomeres and ischemic disease, several recent large population studies now provide particularly compelling data, including an association with cardiovascular mortality. In addition, whether short leukocyte telomeres might be causally related to ischemic disease has been interrogated using Mendelian randomization strategies, which point to shorter leukocyte telomeres as a determining risk factor. Importantly however, the wide, interindividual variability in telomere length still means that a single assessment of leukocyte telomere length in an individual does not reliably report on a biological aging process. In this regard, recent multi-tissue analyses of telomere length dynamics are providing both new mechanistic insights into how telomere length and shortening rates may participate in atherogenesis and risk prediction opportunities. The balance of evidence indicates that short leukocyte telomeres confer a risk for atherosclerotic cardiovascular disease. Moreover, an integrated analysis of telomere lengths in leukocytes and other tissues may provide a window into individualized telomere dynamics, raising new prospects for risk management.
本研究旨在探讨端粒长度与动脉粥样硬化缺血性疾病之间的关联证据。
目前,已有多种策略被用于测量端粒长度,包括分析基因组序列数据和利用与端粒长度相关的基因组位点。这些策略与更为成熟的方法一起,为端粒长度与缺血性疾病之间的关系提供了更全面的认识。尽管早期的荟萃分析表明白细胞端粒较短与缺血性疾病有关,但最近的几项大型人群研究提供了特别有说服力的数据,包括与心血管死亡率的关联。此外,利用孟德尔随机化策略来探究白细胞端粒较短是否与缺血性疾病存在因果关系,该策略指出白细胞端粒较短是一个决定风险的因素。然而,重要的是,端粒长度的个体间广泛差异意味着个体白细胞端粒长度的单次评估并不能可靠地反映生物学衰老过程。在这方面,最近对端粒长度动态的多组织分析为端粒长度和缩短率如何参与动脉粥样硬化形成以及风险预测机会提供了新的机制见解。现有证据表明,白细胞端粒较短与动脉粥样硬化性心血管疾病的风险相关。此外,对白细胞和其他组织中端粒长度的综合分析可能为个体端粒动力学提供一个窗口,为风险管理带来新的前景。