Telomere G-tail Length is a Promising Biomarker Related to White Matter Lesions and Endothelial Dysfunction in Patients With Cardiovascular Risk: A Cross-sectional Study

Tomohisa Nezu,Naohisa Hosomi,Tetsuya Takahashi,Kumiko Anno,Shiro Aoki,Akira Shimamoto,Hirofumi Maruyama,Tomonori Hayashi,Masayasu Matsumoto,Hidetoshi Tahara

doi:10.1016/j.ebiom.2015.05.025

Abstract

BackgroundThe 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. MethodsPatients with a history of cerebrovascular disease and comorbidity were enrolled (n=102; 69 males and 33 females, 70.1±9.2years). 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). FindingsShortened 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. InterpretationTelomere 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.

Highlights

Telomeres are the structures which cap each end of a chromatid, at the extreme end of chromosomal deoxyribonucleic acid (DNA)
We found that telomere G-tail length might be superior to total telomere length as a marker of endothelial dysfunction and age-related white matter changes among patients with cardiovascular risk factors
We demonstrated that the telomere G-tail length of leukocytes is significantly correlated with the endothelial function and severity of agerelated white matter changes (ARWMCs) after adjustment for age, sex, traditional vascular risk factors and laboratory findings

Summary

Introduction

Telomeres are the structures which cap each end of a chromatid, at the extreme end of chromosomal deoxyribonucleic acid (DNA). We found that telomere G-tail length might be superior to total telomere length as a marker of endothelial dysfunction and age-related white matter changes among patients with cardiovascular risk factors. These factors are responsible for dementia, stroke and disability. We investigated the association between the telomere G-tail length of leukocytes and cardiovascular risk, agerelated white matter changes (ARWMCs), and endothelial function. Interpretation: 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

Methods

Results

Conclusion