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Analyses of gastrocnemius muscle biopsies from 113 individuals with PAD [mean ankle-brachial index (ABI)\u00a0=\u00a00.65\u00a0\u00b1\u00a00.13, 38 (33.6%) women, 76 (67.2%) Black] showed a wide range of myofiber type distributions (9.6%-82.6% type 1 myofibers). The abundance of oxidative type 1 myofibers negatively correlated with ABI (r = \u22120.22, P\u00a0=\u00a00.02), a measure of PAD severity. The abundance of type 1 myofibers also negatively correlated to 2a\/x myofiber abundance (r = \u22120.76, P\u00a0&amp;lt;\u00a00.001). Eighty % of participants had NCAM+\u00a0myofibers, a potential indicator of myofiber denervation. Overall, 3.2% of total myofibers were NCAM+. Of 113 muscle biopsies, 86 (76.1%) contained type 1 myofibers with regions lacking intermyofibrillar mitochondria (IMFM-), which may represent formation of target myofibers. In type 1 myofiber IMFM- areas, 77.8% contained 2x myosin heavy chain and\/or the autophagy marker LC3. Electron microscopy within one muscle with IMFM- myofibers confirmed sarcomere disruption in IMFM- regions. These analyses support the possibility of type 2 myofibers transitioning to type 1 in PAD and suggest IMFM- target fibers may represent visualization of this process for the first time. Because type 1 myofibers are more resistant to oxidative damage, results suggest the possibility that a higher proportion of type 1 myofibers in PAD with increasing disease severity may be a compensatory mechanism to maintain muscle.<\/jats:p>","DOI":"10.1093\/function\/zqaf047","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T11:56:39Z","timestamp":1759406199000},"source":"Crossref","is-referenced-by-count":0,"title":["Gastrocnemius Myofiber Type and Mitochondrial Alterations Associated With Peripheral Artery Disease Severity"],"prefix":"10.1152","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5247-4684","authenticated-orcid":false,"given":"Kate","family":"Kosmac","sequence":"first","affiliation":[{"name":"Augusta University College of Allied Health Sciences, Department of Physical Therapy, , Augusta, GA, 30912 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rena Dana","family":"Wang","sequence":"additional","affiliation":[{"name":"University of Kentucky Department of Biostatistics, College of Public Health, , Lexington, KY, 40506 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jada","family":"Stewart","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology, University of Kentucky , Lexington, KY, 40506 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parminder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Augusta University College of Allied Health Sciences, Department of Physical Therapy, , Augusta, GA, 30912 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4025-3945","authenticated-orcid":false,"given":"Ahmed","family":"Ismaeel","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology, University of Kentucky , Lexington, KY, 40506 ,","place":["USA"]},{"name":"University of Kentucky Department of Physiology, College of Medicine, , Lexington, KY, 40506 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haseeb","family":"Ahsan","sequence":"additional","affiliation":[{"name":"Augusta University College of Allied Health Sciences, Department of Physical Therapy, , Augusta, GA, 30912 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Hartnell","sequence":"additional","affiliation":[{"name":"National Institute on Aging , Baltimore, MD, 21224 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther E","family":"Dupont-Versteegden","sequence":"additional","affiliation":[{"name":"Center for Muscle Biology, University of Kentucky , Lexington, KY, 40506 ,","place":["USA"]},{"name":"University of Kentucky Department of Physiology, College of Medicine, , Lexington, KY, 40506 ,","place":["USA"]},{"name":"University of Kentucky Department of Physical Therapy, College of Health Sciences, , Lexington, KY, 40506 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M","family":"McDermott","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine Department of Medicine, , Chicago, IL, 60611 ,","place":["USA"]},{"name":"Northwestern University Feinberg School of Medicine Department of Preventive Medicine, , Chicago, IL, 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L","family":"Sufit","sequence":"additional","affiliation":[{"name":"Northwestern University Feinberg School of Medicine Department of Neurology, , Chicago, IL, 60611 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Ferrucci","sequence":"additional","affiliation":[{"name":"National Institute on Aging , Baltimore, MD, 21224 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