Abstract 18621: Association of Diabetes Mellitus and Clinical Atherosclerosis with Mitochondrial DNA Damage
Mitochondria are recognized as an important source of oxidants that may contribute to vascular disease in diabetes mellitus (DM). Mitochondrial DNA (mtDNA) is particularly sensitive to oxidative damage. In turn, mitochondrial DNA damage leads to mitochondrial dysfunction and increased mitochondrial oxidant production. We sought to evaluate the relation of DM and clinical atherosclerotic disease (coronary artery disease and/or peripheral artery disease) to mtDNA damage in patients. We enrolled 266 patients (age 57±9 years, 60% women) with atherosclerosis alone (N=55), DM alone (N=70), combined atherosclerosis and DM (N=43), and controls age>45 without DM or atherosclerosis (N=98). We measured mtDNA damage in peripheral blood mononuclear cells using quantitative PCR which is based upon the principle that the DNA polymerase is blocked by lesions resulting in a loss of PCR product. The mtDNA lesion frequency (LF) is calculated as the ratio of the amplified product of the majority of the mtDNA (16kb) to that of a small section allowing for normalization to copy number (0.2kb). As shown in the Figure, mtDNA damage levels were higher in each of the 3 patient groups as compared to controls. In bivariate analyses, there were no significant associations of additional cardiovascular risk factors including age, sex, body-mass index, hypertension, hyperlipidemia, or smoking with mtDNA damage levels. In multivariable models adjusting for age and sex and relevant cardiovascular risk factors, a significant association persisted for DM (β=0.27±0.11, P=0.01) but not atherosclerosis (β=0.14±0.11, P=0.23) with mtDNA damage levels. Our findings demonstrate increased mtDNA damage in patients with DM and are consistent with the possibility that DM triggers mitochondrial damage that may promote oxidative stress. Further study is required to identify the mechanisms of mtDNA damage in patients with DM and to investigate the potential links to vascular dysfunction and atherogenesis.
Author Disclosures: J.L. Fetterman: None. S.W. Ballinger: None. M. Holbrook: None. D.G. Westbrook: None. J.A. Brown: None. K.P. Feeley: None. B.D. Berk: None. E.A. Linder: None. M.E. Widlansky: None. P. Dorsey: None. R. Leleiko: None. B. Feng: None. N. Gokce: None. N.M. Hamburg: None. J.A. Vita: None.
- © 2014 by American Heart Association, Inc.