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Figure 1.

Flowchart of intervention assignment of HF patients.

*Skeletal muscle biopsies were not taken from these patients, therefore, they were excluded from analysis.

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Table 1.

α2A2CARKO mice physiological parameters.

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Figure 2.

Plantaris trophicity, oxidative stress and chymotrypsin-like proteasomal activity in α2A2CARKO mice.

Plantaris muscle cross-sectional area (CSA) (A), lipid hydroperoxidation (B), protein carbonylation (C) and chymotrypsin-like proteasome activity (D) in 3, 5 and 7 month-old wild type (WT) and α2A2CARKO mice (ARKO). Immunobloting data are shown as percentage of age-matched WT group (set to 100%)). Representative images of immunoblots are shown below respective charts. Data are presented as mean ± standard error from mean. *p<0.05 vs. age-matched WT.

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Table 2.

Cardiac function and lung water content.

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Table 2 Expand

Figure 3.

mRNA levels of UPS components.

mRNA levels of E3 ligases E3-α, MuRF-1 and Atrogin-1 (A), and deubiquitinating enzymes USP28, USP19 and USP14 (B). WT values were arbitrarily set to 1.0 and are represented by the dashed line. Data are shown as fold change over wild type control group and presented as mean ± standard error from mean. *p<0.05 vs. WT; #p<0.05 vs. age-matched ARKO.

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Figure 4.

UPS activation and effects of AET.

Protein ubiquitination (A), chymotrypsin-like proteasome activity (B) and protein carbonylation (C) in 7 month-old wild type (WT), untrained α2A2CARKO (ARKO) and trained α2A2CARKO mice (ARKOT). Representative images of immunoblots are shown below respective charts. Data are shown as percentage of WT control group values (set to 100%) and presented as mean ± standard error from mean. *p<0.05 vs. age-matched WT; #p<0.05 vs. age-matched ARKO.

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Figure 4 Expand

Figure 5.

Skeletal muscle structure and global function

. Plantaris cross-sectional area (CSA) (A), running performance (B) and time on rotarod (C) in 7 month-old wild type (WT), untrained α2A2CARKO (ARKO) and trained α2A2CARKO mice (ARKOT). Data are presented as mean ± standard error from mean. *p<0.05 vs. age-matched WT; #p<0.05 vs. age-matched ARKO.

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Table 3.

Patient physiological parameters.

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Table 3 Expand

Figure 6.

Skeletal muscle UPS in human HF.

Chymotrypsin-like proteasome activity (A) and protein ubiquitination (B) and carbonylation (C) in healthy control subjects (Control), sedentary (HF-S) and trained HF (HF-T) patients. Immunobloting data are shown as percentage of Control group (set to 100%). Data are presented as mean ± standard error from mean. *p<0.05 vs. Control.

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