Abstract 655: Increased Nadph-Oxidase Activity Is Associated With Reduced Telomere Length in the Human Vascular Wall: The Influence of Oxidative Stress on Biological Aging
Background: Accelerated telomere shortening is a hallmark of cellular senescence and has been associated with cardiovascular disease (CVD). Oxidative stress has been proposed as a cause of telomere damage. We explored the association between vascular redox state and telomere length in patients with advanced atherosclerosis.
Methods: We recruited xx patients undergoing bypass surgery. Saphenous vein (SV) samples were used to measure superoxide (O2-) generation using lucigenin chemiluminescence (+NADPH 100 uM to estimate NADPH-oxidase activity). DNA was extracted from whole-blood and SV samples and used to measure relative telomere length (TL) using qPCR (which determines T/S ratio using albumin as a single-copy gene). DNA was also used to genotype for two functional single nucleotide polymorphisms (SNPs rs4673 and rs1049255) in the CYBA locus, which encodes for the p22phox membrane subunit of NADPH-oxidase and is associated with activity of the enzyme.
Results: Shorter vascular TL was associated with increased NADPH-stimulated O2- generation in SV tissue (A). The additive effect of the rs4673C and rs1049255G alleles was linked to increased vascular NADPH-oxidase activity (B). In addition, the same combination of SNP alleles was linked to reduced T/S ratio in whole blood DNA (C), suggesting a causal association between high oxidative stress and accelerated telomere shortening.
Conclusions: We demonstrate for the first time in humans that genetically determined high NADPH-oxidase activity could be causally linked to reduced TL in vascular and blood cells. These novel findings highlight the importance of oxidative stress on cellular senescence and provide an important link between aging and cardiovascular disease.
Author Disclosures: M. Margaritis: None. S. Patel: None. A.S. Antonopoulos: None. L. Herdman: None. F. Sanna: None. K. Ananthan: None. M. Petrou: None. G. Krasopoulos: None. K.M. Channon: None. C. Antoniades: None.
- © 2015 by American Heart Association, Inc.