Abstract W P361: Telomere G-tail Length Shortening is Associated With Endothelial Dysfunction in Patients With Chronic Cerebrovascular Disease and Comorbidity
Background and Purpose: Telomere length of leukocytes is associated with cardiovascular risk as well as ischemic stroke and poststroke mortality. In addition, leukocyte telomere length shortening is thought to be associated with increased carotid intimal medial thickness (IMT) and endothelial dysfunction evaluated by flow mediated dilation (FMD). Recently, telomeric 3’-overhang (G-tail) lengths has been essential for the biological effects of telomere dysfunction. The aim of this study was to investigate the associations between telomere G-tail lengths of leukocytes and the physiological studies.
Methods: Patients with cerebrovascular diseases history and other neurological problems were enrolled in this study (n=63; 39 male, 69.8±10.0 years). Telomere G-tail lengths were measured by G-tail telomere hybridization protection assay (H Tahara et al. Nat Methods. 2005). The mean value of maximal IMT measured in the distal CCA far wall (CCA-IMT) and plaque score were measured by carotid ultrasonography. Endothelial dysfunction was defined as a FMD≤4.5%.
Results: Telomere G-tail length (18947.0±4066.6 RLU/μg DNA) was positively correlated with total telomere length (230330.8±25830.9 RLU/μg DNA; R2=0.261, p<0.001). In addition, telomere G-tail length was negatively correlated with age (R2=0.217, p<0.001) and positively correlated with FMD (R2=0.136, p=0.003). Telomere G-tail length was not related to CCA-IMT and plaque score. The patients with endothelial dysfunction (n=39, 61.9%) were older (72.4±7.6 vs. 65.5±11.8, P=0.007), more frequently male (74.4% vs. 41.7%, P=0.016) and more frequently had hypertension (89.7% vs. 37.5%, P<0.001) than the patients without. After multivariate analysis with age, sex, presence of stroke and comorbidities, the lowest quartile of telomere G-tail length was independently associated with the endothelial dysfunction (OR 3.85, 95%CI 1.58-12.42, P=0.002), although there was no significant association between total telomere length and endothelial dysfunction on multivariate analysis.
Conclusion: Telomere G-tail length might be more useful marker for the endothelial dysfunction which was evaluated by FMD than total telomere length.
Author Disclosures: T. Nezu: None. N. Hosomi: None. S. Aoki: None. T. Takahashi: None. K. Anno: None. H. Maruyama: None. Y. Higashi: None. H. Tahara: None. M. Matsumoto: None.
- © 2014 by American Heart Association, Inc.