端粒长度和线粒体 DNA 拷贝数与生物衰老的两个生物标志物与静脉血栓栓塞风险的关联。

Association of telomere length and mitochondrial DNA copy number, two biomarkers of biological aging, with the risk of venous thromboembolism.

机构信息

Clinical Division of Haematology and Haemostaseology, Department of Medicine I, Medical University of Vienna; Vienna, Austria.

Center for Biomedical Research, Medical University of Vienna, Vienna, Austria; Ludwig Boltzmann Institute for Cardiovascular Research, Medical University of Vienna, Vienna, Austria.

出版信息

Thromb Res. 2023 Mar;223:168-173. doi: 10.1016/j.thromres.2023.01.031. Epub 2023 Feb 3.

DOI:10.1016/j.thromres.2023.01.031

PMID:36758285

Abstract

BACKGROUND

Venous thromboembolism (VTE) is the third most common cardiovascular disease and occurs in all age groups, albeit the risk increases considerably with age. Previous research indicates mitochondrial dysfunction and telomere shortening in cardiovascular aging. However, in the context of VTE this has not been investigated in detail.

AIM

We aimed to explore biomarkers reflecting biological aging (i.e. human mitochondrial DNA copy number (mtDNA) and telomere length) and their association with VTE.

METHODS

mtDNA and telomere length were measured in a case-control study of 116 patients with a history of VTE and 128 age- and sex-matched healthy individuals from isolated blood using a qPCR-based assay kit. Cases had at least one unprovoked VTE event and were enrolled no earlier than 3 months after the last VTE event.

RESULTS

The mtDNA copy number was significantly lower in VTE cases compared to controls (median [IQR]: 663 per diploid cells [78.75-2204.5] vs. 2832 per diploid cells [724-4350]; p < 0.001). After adjustment for age, sex, BMI, and smoking, mtDNA copy number was independently associated with VTE risk (odds ratio per increase in 400 mtDNA per diploid cell: 0.889, 95%CI 0.834-0.947). mtDNA copy numbers were significantly different between women and men (2375 [455-3737] women vs. 893 [152-3154] men; p < 0.001). The analysis of telomere length showed no significant difference between patients and healthy controls.

CONCLUSION

Lower mtDNA levels were found in patients with VTE compared to controls, indicating an association of biological aging with risk of VTE.

摘要

背景

静脉血栓栓塞症（VTE）是第三大常见心血管疾病，可发生于所有年龄段，但风险随年龄增长显著增加。先前的研究表明，线粒体功能障碍和端粒缩短与心血管衰老有关。然而，在 VTE 方面，这方面尚未得到详细研究。

目的

我们旨在探讨反映生物衰老的生物标志物（即人线粒体 DNA 拷贝数（mtDNA）和端粒长度）及其与 VTE 的关联。

方法

在一项病例对照研究中，我们使用基于 qPCR 的检测试剂盒，从 116 例有 VTE 病史的患者和 128 例年龄和性别匹配的健康个体的分离血液中测量了 mtDNA 和端粒长度。病例至少有一次无诱因的 VTE 事件，且在最后一次 VTE 事件后不少于 3 个月入组。

结果

VTE 病例的 mtDNA 拷贝数明显低于对照组（中位数 [IQR]：663 个每个二倍体细胞 [78.75-2204.5] 与 2832 个每个二倍体细胞 [724-4350]；p<0.001）。在校正年龄、性别、BMI 和吸烟因素后，mtDNA 拷贝数与 VTE 风险独立相关（每个二倍体细胞增加 400 mtDNA 的比值比：0.889，95%CI 0.834-0.947）。女性和男性的 mtDNA 拷贝数差异有统计学意义（女性 2375 [455-3737] 与男性 893 [152-3154]；p<0.001）。端粒长度分析显示患者与健康对照组之间无显著差异。