Department of Clinical Neuroscience and Therapeutics, Hiroshima University Graduate School of Biomedical and Health Sciences, Hiroshima, Japan.
Department of Cellular and Molecular Biology, Institute of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan.
EBioMedicine. 2015 May 30;2(8):960-7. doi: 10.1016/j.ebiom.2015.05.025. eCollection 2015 Aug.
The telomeric 3'-overhang (G-tail) length is essential for the biological effects of telomere dysfunction in vitro, but the association of length with aging and cardiovascular risk is unclear in humans. We investigated the association between the telomere G-tail length of leukocytes and cardiovascular risk, age-related white matter changes (ARWMCs), and endothelial function.
Patients with a history of cerebrovascular disease and comorbidity were enrolled (n = 102; 69 males and 33 females, 70.1 ± 9.2 years). Total telomere and telomere G-tail lengths were measured using a hybridization protection assay. Endothelial function was evaluated by ultrasound assessment of brachial flow-mediated dilation (FMD).
Shortened telomere G-tail length was associated with age and Framingham risk score (P = 0.018 and P = 0.012). In addition, telomere G-tail length was positively correlated with FMD values (P = 0.031) and negatively with the severity of ARWMCs (P = 0.002). On multivariate regression analysis, telomere G-tail length was independently associated with FMD values (P = 0.022) and the severity of ARWMCs (P = 0.033), whereas total telomere length was not associated with these indicators.
Telomere G-tail length is associated with age and vascular risk factors, and might be superior to total telomere length as a marker of endothelial dysfunction and ARWMC severity.
端粒 3'-突出端(G-尾)长度对于体外端粒功能障碍的生物学效应至关重要,但在人类中,其长度与衰老和心血管风险的关联尚不清楚。我们研究了白细胞端粒 G-尾长度与心血管风险、与年龄相关的白质改变(ARWMCs)和内皮功能之间的关系。
纳入有脑血管疾病病史和合并症的患者(n=102;69 名男性和 33 名女性,70.1±9.2 岁)。使用杂交保护测定法测量总端粒和端粒 G-尾长度。通过超声评估肱动脉血流介导的扩张(FMD)来评估内皮功能。
端粒 G-尾长度缩短与年龄和弗雷明汉风险评分相关(P=0.018 和 P=0.012)。此外,端粒 G-尾长度与 FMD 值呈正相关(P=0.031),与 ARWMC 严重程度呈负相关(P=0.002)。多元回归分析显示,端粒 G-尾长度与 FMD 值(P=0.022)和 ARWMC 严重程度(P=0.033)独立相关,而总端粒长度与这些指标无关。
端粒 G-尾长度与年龄和血管危险因素相关,作为内皮功能障碍和 ARWMC 严重程度的标志物,可能优于总端粒长度。