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- Title
Mitochondrial DNA damage and vascular function in patients with diabetes mellitus and atherosclerotic cardiovascular disease.
- Authors
Fetterman, Jessica L.; Holbrook, Monica; Westbrook, David G.; Brown, Jamelle A.; Feeley, Kyle P.; Bretón‑Romero, Rosa; Linder, Erika A.; Berk, Brittany D.; Weisbrod, Robert M.; Widlansky, Michael E.; Gokce, Noyan; Ballinger, Scott W.; Hamburg, Naomi M.
- Abstract
Objective: Prior studies demonstrate mitochondrial dysfunction with increased reactive oxygen species generation in peripheral blood mononuclear cells in diabetes mellitus. Oxidative stress-mediated damage to mitochondrial DNA promotes atherosclerosis in animal models. Thus, we evaluated the relation of mitochondrial DNA damage in peripheral blood mononuclear cells s with vascular function in patients with diabetes mellitus and with atherosclerotic cardiovascular disease. Approach and results: We assessed non-invasive vascular function and mitochondrial DNA damage in 275 patients (age 57 ± 9 years, 60 % women) with atherosclerotic cardiovascular disease alone (N = 55), diabetes mellitus alone (N = 74), combined atherosclerotic cardiovascular disease and diabetes mellitus (N = 48), and controls age >45 without diabetes mellitus or atherosclerotic cardiovascular disease (N = 98). Mitochondrial DNA damage measured by quantitative PCR in peripheral blood mononuclear cells was higher with clinical atherosclerosis alone (0.55 ± 0.65), diabetes mellitus alone (0.65 ± 1.0), and combined clinical atherosclerosis and diabetes mellitus (0.89 ± 1.32) as compared to control subjects (0.23 ± 0.64, P < 0.0001). In multivariable models adjusting for age, sex, and relevant cardiovascular risk factors, clinical atherosclerosis and diabetes mellitus remained associated with higher mitochondrial DNA damage levels (β = 0.14 ± 0.13, P = 0.04 and β = 0.21 ± 0.13, P = 0.002, respectively). Higher mitochondrial DNA damage was associated with higher baseline pulse amplitude, a measure of arterial pulsatility, but not with flow-mediated dilation or hyperemic response, measures of vasodilator function. Conclusions: We found greater mitochondrial DNA damage in patients with diabetes mellitus and clinical atherosclerosis. The association of mitochondrial DNA damage and baseline pulse amplitude may suggest a link between mitochondrial dysfunction and excessive small artery pulsatility with potentially adverse microvascular impact.
- Subjects
ATHEROSCLEROSIS; MITOCHONDRIAL DNA abnormalities; REACTIVE oxygen species; DIABETES; OXIDATIVE stress; PEOPLE with diabetes; CARDIOVASCULAR diseases
- Publication
Cardiovascular Diabetology, 2016, Vol 15, p1
- ISSN
1475-2840
- Publication type
Article
- DOI
10.1186/s12933-016-0372-y