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oai:repisalud.isciii.es:20.500.12105/230442024-11-28T19:39:55Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16967

00925njm 22002777a 4500 dc Gonzalez-Freire, Marta author Moore, A. Zenobia author Peterson, Charlotte A author Kosmac, Kate author McDermott, Mary M author Sufit, Robert L author Guralnik, Jack M author Polonsky, Tamar author Tian, Lu author Kibbe, Melina R author Criqui, Michael H author Li, Lingyu author Leeuwenburgh, Christian author Ferrucci, Luigi author 2020-04-09 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. Gonzalez-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. 2047-9980 http://hdl.handle.net/20.500.13003/17129 https://hdl.handle.net/20.500.12105/23044 32200714 10.1161/JAHA.119.015197 Journal of the American Heart Association 2-s2.0-85082260170 527597700044 L631311653 Ankle brachial index D-loop Heteroplasmy mtDNA mtDNA copy number Peripheral artery disease Associations of Peripheral Artery Disease With Calf Skeletal Muscle Mitochondrial DNA Heteroplasmy