Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/17129
Associations of Peripheral Artery Disease With Calf Skeletal Muscle Mitochondrial DNA Heteroplasmy
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CitationGonzalez-Freire M, Moore AZ, Peterson CA, Kosmac K, Mcdermott MM, Sufit RL, et al. Associations of Peripheral Artery Disease With Calf Skeletal Muscle Mitochondrial DNA Heteroplasmy. J Am Heart Assoc. 2020 Apr 09;9(7). Epub 2020 Mar 21.
Background Patients with peripheral artery disease (PAD) undergo frequent episodes of ischemia-reperfusion in lower extremity muscles that may negatively affect mitochondrial health and are associated with impaired mobility. We hypothesized that skeletal muscle from PAD patients will show high mitochondrial DNA heteroplasmy, especially in regions more susceptible to oxidative damage, such as the displacement loop, and that the degree of heteroplasmy will be correlated with the severity of ischemia and mobility impairment. Methods and Results Mitochondrial mutations and deletions and their relative abundance were identified by targeted mitochondrial DNA sequencing in biopsy specimens of gastrocnemius muscle from 33 PAD (ankle brachial index <0.9) and 9 non-PAD (ankle brachial index >0.9) subjects aged >= 60 years. The probability of heteroplasmy per DNA base was significantly higher for PAD subjects than non-PAD within each region. In adjusted models, PAD was associated with higher heteroplasmy than non-PAD (P=0.003), but the association was limited to microheteroplasmy, that is heteroplasmy found in 1% to 5% of all mitochondrial genomes (P=0.004). Heteroplasmy in the displacement loop and coding regions were significantly higher for PAD than non-PAD subjects after adjustment for age, sex, race, and diabetes mellitus (P=0.037 and 0.004, respectively). Low mitochondrial damage, defined by both low mitochondrial DNA copy number and low microheteroplasmy, was associated with better walking performance. Conclusions People with PAD have higher low frequency heteroplasmy in gastrocnemius muscle compared with people without PAD. Among people with PAD, those who had evidence of least mitochondrial damage, had better walking performance than those with more mitochondrial damage. Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02246660.
Randomized Controlled Trials as Topic
Severity of Illness Index
Peripheral Arterial Disease
Persona de Mediana Edad
Enfermedad Arterial Periférica
Índice de Severidad de la Enfermedad
Limitación de la Movilidad
Ensayos Clínicos Controlados Aleatorios como Asunto
Estudios de Casos y Controles