{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T21:53:02Z","timestamp":1781214782476,"version":"3.54.1"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,4,9]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Patients with peripheral artery disease (PAD) undergo frequent episodes of ischemia\u2010reperfusion 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              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 &lt;0.9) and 9 non\u2010PAD (ankle brachial index &gt;0.9) subjects aged \u226560\u00a0years. The probability of heteroplasmy per DNA base was significantly higher for PAD subjects than non\u2010PAD within each region. In adjusted models, PAD was associated with higher heteroplasmy than non\u2010PAD (\n              <jats:italic>P<\/jats:italic>\n              =0.003), but the association was limited to microheteroplasmy, that is heteroplasmy found in 1% to 5% of all mitochondrial genomes (\n              <jats:italic>P<\/jats:italic>\n              =0.004). Heteroplasmy in the displacement loop and coding regions were significantly higher for PAD than non\u2010PAD subjects after adjustment for age, sex, race, and diabetes mellitus (\n              <jats:italic>P<\/jats:italic>\n              =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.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">People with PAD have higher \u201clow frequency\u201d 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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Registration<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.clinicaltrials.gov\">http:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              . Unique identifier: NCT02246660.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.119.015197","type":"journal-article","created":{"date-parts":[[2020,3,21]],"date-time":"2020-03-21T09:00:23Z","timestamp":1584781223000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":29,"title":["Associations of Peripheral Artery Disease With Calf Skeletal Muscle Mitochondrial DNA Heteroplasmy"],"prefix":"10.1161","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9741-2826","authenticated-orcid":false,"given":"Marta","family":"Gonzalez\u2010Freire","sequence":"first","affiliation":[{"name":"National Institutes on Health National Institute on Aging Baltimore MD"},{"name":"Health Research Institute of the Balearic Islands (IdISBa) Palma de Mallorca Illes Balears Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. Zenobia","family":"Moore","sequence":"additional","affiliation":[{"name":"National Institutes on Health National Institute on Aging Baltimore MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte A.","family":"Peterson","sequence":"additional","affiliation":[{"name":"College of Health Sciences and Center for Muscle Biology University of Kentucky Lexington KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Kosmac","sequence":"additional","affiliation":[{"name":"College of Health Sciences and Center for Muscle Biology University of Kentucky Lexington KY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"McDermott","sequence":"additional","affiliation":[{"name":"Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL"},{"name":"Department of Preventive Medicine Northwestern University Feinberg School of Medicine Chicago 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School of Medicine Chapel Hill NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Criqui","sequence":"additional","affiliation":[{"name":"Department of Family Medicine and Public Health University of California at San Diego La Jolla CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medicine Northwestern University Feinberg School of Medicine Chicago IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Leeuwenburgh","sequence":"additional","affiliation":[{"name":"Department of Aging and Geriatric Research University of Florida Institute on Aging Gainesville FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Ferrucci","sequence":"additional","affiliation":[{"name":"National Institutes on Health National Institute on Aging Baltimore 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