Table 1.
Treatment groups based on combinations of cholesterol level, exercise, and statin treatment over days 1–14 and days 15–28.
Table 2.
Body Weight.
Fig 1.
Effect of statin treatment and exercise on cholesterol, voluntary running wheel activity, and maximal grip strength.
ApoE-/- mice were evaluated following normal cage activity (Sedentary), two weeks of wheel running in combination with saline or simvastatin (20 mg/kg) (Novel), or two weeks of wheel running in combination with saline or simvastatin after two weeks of exercise training (Accustomed). (A) Cholesterol level at the end of the intervention, (B) running wheel distance for novel exercise group, (C) running wheel distance for accustomed group, (D) grip strength, and (E) change in grip strength from beginning to end of study. E: ApoE-/-, Z: Zocor (simvastatin), S: Saline, S: Sedentary, N: Novel, A: Accustomed. Means ± SD; n = 8-10/group. † = main effect of statin, p<0.05; # = statin x time interaction, p<0.05; * = within group pairwise comparison, p<0.05.
Fig 2.
Effect of statin treatment and exercise on maximal isometric force.
The sciatic nerve of ApoE-/- mice was stimulated and hindlimb isometric force was evaluated following normal cage activity (Sedentary), two weeks of wheel running in combination with saline or simvastatin (20 mg/kg) (Novel), or two weeks of wheel running in combination with saline or simvastatin after two weeks of exercise training (Accustomed). (A) Maximal isometric force, (B) maximal isometric force produced with repeated stimulation to provide a measure of fatigability, (C) difference in force between initial stimulation and after 10 events to provide a measure of fatigability. E: ApoE-/-, Z: Zocor (simvastatin), S: Saline, S: Sedentary, N: Novel, A: Accustomed. Means ± SD; n = 8-10/group. † = main effect of statin, p<0.05; # = time main effect, p<0.05; * = within group pairwise comparison, p<0.05.
Fig 3.
Statin treatment prevents beneficial adaptations obtained following accustomed exercise.
(A) PGC-1α mRNA and (B) mitochondrial DNA content in gastrocnemius muscles, and (C) plasma 4-HNE after normal cage activity (Sedentary), two weeks of wheel running in combination with saline or simvastatin (20 mg/kg) (Novel), or two weeks of wheel running in combination with saline or simvastatin after two weeks of exercise training (Accustomed). Means ± SD; n = 8-10/group. † = main effect of statin p<0.05; § = statin x exercise interaction, p<0.05; a,b,c = different letters indicate statistically significant differences at 95% confidence.
Fig 4.
Statin treatment in combination with novel or accustomed exercise increases serum amyloid A content and atrogin-1 gene expression in skeletal muscle, but does not increase fiber damage or impact fiber repair.
(A) Serum amyloid A content and (B) atrogin-1 mRNA, (C) IgG+ myofibers, and (D) CLN+ myofibers in gastrocnemius muscles after normal cage activity (Sedentary), two weeks of wheel running in combination with saline or simvastatin (20 mg/kg) (Novel), or two weeks of wheel running in combination with saline or simvastatin after two weeks of exercise training (Accustomed). Representative images of IgG+ and CLN+ fibers in muscle are presented for (C) and (D). Means ± SD; n = 8-10/group. § = statin x exercise interaction, p<0.05; † = main effect of statin, p<0.05; * = within group pairwise comparison, p<0.05.
Fig 5.
Statin treatment does not significantly impact fiber type specific cross sectional area.
(A) Average myofiber CSA (all types combined), (B) representative image of CSA staining, (C) average Type 2A CSA, (D) average Type 2B CSA, and (E) average Type 2X CSA after normal cage activity (Sedentary), two weeks of wheel running in combination with saline or simvastatin (20 mg/kg) (Novel), or two weeks of wheel running in combination with saline or simvastatin after two weeks of exercise training (Accustomed). Representative images of fiber types in muscle are presented for (E). Means ± SD; n = 4-6/group. § = statin x exercise interaction, p<0.05; a,b = different letters indicate statistically significant differences at 95% confidence.