Abstract 17377: Tissue-Specific Telomere Length Variability Predicts Vascular Oxidative Stress in Human Arteries and Veins
Background: Telomere length (TL) shortening has been related to atherogenesis, and in vitro data suggest that oxidative stress reduces TL in vascular cells. We explored the value of TL measurement in peripheral blood as a marker of vascular redox state in humans.
Methods: We recruited 648 patients undergoing CABG. Superoxide (O2-) production was measured by lucigenin chemiluminescence in vascular segments of internal mammary artery (IMA), saphenous vein (SV) and peripheral blood mononuclear cells (PBMNCs), by using NADPH 100 uM ± NADPH-oxidase inhibitor Vas2870 and ±LNAME (to determine endothelial nitric oxide synthase (eNOS) coupling status). Telomere to single copy gene ratio (T/S) was measured in peripheral blood DNA by qPCR in the entire cohort. In a sub-group of 35 patients T/S was measured also in DNA extracted from SV and IMA segments. Systemic oxidative stress was evaluated by measuring plasma malonyldialdehyde (MDA) levels.
Results: Whole blood TL was not associated with resting (A) or NADPH-stimulated O2- generation in SVs or IMAs. Similarly, whole blood TL was not associated with NADPH-stimulated or Vas2870-inhibitable O2- in PBMNCs, but significantly with plasma MDA levels (P<0.01). There was a strong negative correlation between vascular TL and resting as well as NADPH-stimulated O2- in IMAs (B&C) and SVs (p<0.01 and p<0.05 respectively). In addition, a strong positive correlation was observed between LNAME-inhibitable O2- and vascular TL in IMAs (D) and SVs (p<0.01), linking high vascular TL and improved coupling of eNOS.
Conclusions: We clearly demonstrate that whole-blood TL is not associated with vascular oxidative stress. On the contrary, TL in human arteries and veins is strongly related to NADPH-oxidase activity and eNOS coupling within the same tissue. These results document significant tissue-specific variability of telomere length, and imply that telomere shortening is more relevant to the biology of the tissue in which it is measured.
Author Disclosures: M. Margaritis: None. S. Patel: None. C. Duke: None. A.S. Antonopoulos: None. L. Herdman: None. R. Sayeed: None. R. Desilva: None. M. Petrou: None. K.M. Channon: None. C. Antoniades: None.
- © 2014 by American Heart Association, Inc.