Biological Age and Circulating Progenitor Cell Levels as Predictors Heart Disease Events.
Biological Age and Circulating Progenitor Cell Levels as Predictors Heart Disease Events.
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生物年龄和循环祖细胞水平作为心脏病事件的预测因子。
DOI：
10.1161/circresaha.117.310698
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发表时间：
2017
影响因子：
20.1
通讯作者：
Cimato,ThomasR
中科院分区：
文献类型：
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作者：
Cimato,ThomasR
Hammadah 等人的研究有一些局限性需要考虑。该研究重点关注总白细胞中的端粒长度，而不是 CD34+ 细胞或更纯化的细胞群。先前的研究表明 LTL 与 HSC 中的端粒长度相关。然而，这仍有待确定。整个骨髓中的端粒磨损并不均匀。 14 端粒长度随着年龄的增长而缩短，淋巴细胞和粒细胞谱系的端粒长度在生命的第一年下降最显着，这表明其前体 HSC 的复制端粒缩短。 14 随着年龄的增长，淋巴细胞中的端粒长度比粒细胞中的端粒长度缩短得更多。 14 在未来的研究中，使用流式 FISH（荧光原位杂交）等单细胞方法测量端粒长度可能会获得更多见解。 14 该研究的第二个局限性是实际考虑。为了将这种方法应用于患者的常规护理，需要来自年龄和性别匹配的无 CAD 受试者的循环 CD34+ 细胞的参考范围。需要在专门针对此目的的研究中定义验证这种方法的研究。总而言之，循环 CD34+ 细胞和 LTL 测量可预测稳定 CAD 患者的 CVD 事件。循环中的 CD34+ 细胞可能代表 CVD 风险因素的传感器，因为 CVD 风险因素对 HSC 具有生物效应，导致可用 CD34+ 细胞减少和端粒缩短。 CVD 危险因素对 LTL 的作用尚不清楚，可能更多地受到遗传因素和青少年时期遇到的压力因素的影响。 LTL 可以被视为细胞复制历史的衡量标准，其中较短的端粒是由较高水平的细胞复制引起的。未来的研究可能会集中于这两种措施在预测无 CAD 的年轻患者中的 CVD 事件风险的效用。最重要的是，这两项衰老和再生能力的衡量标准似乎更接近临床应用，可对稳定型 CAD 患者进行风险分层。
There a few limitations of the study by Hammadah et al1 to be considered. The study focuses on telomere length in total leukocytes and not CD34+ cells, or more purified cell populations. Prior studies indicate LTL correlates with telomere length in HSCs; however, this remains to be determined. Telomeres attrition is not uniform throughout bone marrow. 14 Telomere length declines with age, with the most dramatic drop occurring in the first year of life in both lymphocyte and granulocyte lineages suggesting replicative telomere shortening in their precursors, the HSCs. 14 With increasing age, telomere length in lymphocytes decreases more than in granulocytes. 14 Additional insights may be garnered in future studies using single-cell approaches to measure telomere length such as flow FISH (fluorescence in situ hybridization). 14 A second limitation of the study is a practical consideration. To apply this approach in routine care of patients, a reference range for circulating CD34+ cells from age-and sex-matched subjects without CAD is needed. Studies to validate such an approach would need to be defined in a study tailored to this purpose.To summarize, circulating CD34+ cells and LTL measures were predictive of CVD events in patients with stable CAD. Circulating CD34+ cells may represent a sensor for CVD risk factors, as CVD risk factors have biological effects on HSCs that results in a decline in available CD34+ cells and shortening of telomeres. The role of CVD risk factors on LTL remains less clear and may be more influenced by inherited factors, and stressors encountered during youth. LTL may be viewed as a measure of the replicative history of cells, where shorter telomeres are incurred by higher levels of cell replication. Future studies may focus on the utility of these 2 measures to predict CVD event risk in younger patients without known CAD. Most importantly, these 2 measures of aging and regenerative capacity appear closer to clinical use to risk stratify patients with stable CAD.