Supplemental Files

Supplementary Files for manuscript. <b>Supplementary Table S1. List of abbreviations used in manuscript. </b><b>S</b><b>upplementary Figure S1. Fiber characteristics of skeletal muscle biopsies from COCOA-PAD trial.</b> <b>A-C) </b>Change in average myofiber cross-sectional area (CSA) of Type I <b>(A)</b>, Type IIa <b>(B)</b>, and Type IIa/x <b>(C)</b> fibers from baseline to 6-month follow-up in PLA and COCOA groups. D-F) Change in fiber type frequency, % of total fibers that are Type I <b>(D)</b>, Type IIa <b>(E)</b>, or Type IIa/x <b>(F)</b>. <b>G)</b> Change in the proportion of Type I fibers (%) with central nuclei. Difference between groups tested using an independent t-test, n=5 in PLA, n=9 in COCOA, ns: not significant. <b>Supplementary Figure S2. Correlations between fiber characteristics, muscle measures, and walking performance from COCOA-PAD trial. </b><b>A-B) </b>Association between the fold change in HO-1 levels <b>(A) </b>or NQO1 levels <b>(B)</b> with the change in Type II fibers with central nuclei. <b>(C-D)</b> The association between the fold change in HO-1 levels <b>(C)</b> or NQO1 levels<b> (D) </b>with the fold change in UQCRC2 levels. <b>E)</b> Association between the fold change in UQCRC2 levels and the change in 6-minute walk distance (m) from baseline to 6-month follow-up. Association tested by Pearson correlation. COCOA points shown in green and PLA shown in gray. Line of best fit, R², and p-values shown. <b>Supplementary Figure S3. PAD serum treatment and EPI treatment effects on myotubes. A)</b> OCR trace over time after injections of indicated mitochondrial respiration modulators in Control myotubes [CON, standard 2% horse serum (HS)], 10% pooled PAD serum-treated myotubes (PAD serum), and 10% pooled healthy participant serum-treated myotubes (Healthy serum). <b>B) </b>Quantification of maximal OCR (FCCP-stimulated), normalized to protein concentration. <b>C) </b>Hydrogen peroxide production, assessed by AmR fluorescence. Data expressed as fold-regulation relative to CON myotubes. Experiments are averages of 4 technical replicates. <b>D)</b> Representative Western blot of p-Nrf2 and Nrf2 levels in myotube lysates treated with increasing doses of EPI or sulforaphane (SFN) as a positive control. <b>E)</b> Quantification of p-Nrf2 levels after densitometric analysis of the levels of each sample normalized to corresponding Nrf2 (p-Nrf2/Nrf2), expressed as fold-regulation relative to CON (untreated, 0 μM). Difference between groups (n=2-3/group) tested using a one-way ANOVA, results of pairwise post-hoc analyses (Tukey’s) displayed as *p&lt;0.05, **p&lt;0.01, ***p&lt;0.001. <br>