Show simple item record

dc.contributor.authorGonzalez-Freire, M.
dc.contributor.authorMoore, A.Z.
dc.contributor.authorGuralnik, J.M.
dc.date.accessioned2020-04-03T15:58:15Z
dc.date.available2020-04-03T15:58:15Z
dc.date.issued2020
dc.identifier.urihttps://www.scopus.com/inward/record.uri?eid=2-s2.0-85082260170&doi=10.1161%2fJAHA.119.015197&partnerID=40&md5=bf0aa4256d8436e31b22c57df5e1005a
dc.identifier.urihttp://hdl.handle.net/10713/12477
dc.description.abstractBackground: 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.en_US
dc.description.urihttps://doi.org/10.1161/JAHA.119.015197en_US
dc.language.isoen_USen_US
dc.publisherWiley-Blackwellen_US
dc.relation.ispartofJournal of the American Heart Association
dc.subjectankle brachial indexen_US
dc.subjectD-loopen_US
dc.subjectheteroplasmyen_US
dc.subjectmtDNAen_US
dc.subjectmtDNA copy numberen_US
dc.subjectperipheral artery diseaseen_US
dc.titleAssociations of Peripheral Artery Disease With Calf Skeletal Muscle Mitochondrial DNA Heteroplasmyen_US
dc.typeArticleen_US
dc.identifier.doi10.1161/JAHA.119.015197
dc.identifier.pmid32200714


This item appears in the following Collection(s)

Show simple item record