Effect of Statins on Muscular and Cardiorespiratory Adaptations to Treadmill Training in Hypercholesterolemic Mice

Abstract

Individuals with hypercholesterolemia are at an increased risk for developing heart disease and are commonly prescribed statin medications, the most effective cholesterol‐lowering drugs, as well as exercise. Common adverse effects of statins include muscle pain and/or dysfunction, that may be exacerbated with exercise. Both exercise training and statins have been associated with reductions in inflammatory cytokines such as interleukin‐6 (IL‐6). To date, no studies have investigated if hypercholesterolemia alone impacts muscular and cardiorespiratory adaptations to treadmill training and how statin treatment may alter these adaptations. We hypothesized that hypercholesterolemia alone would impair muscular and cardiorespiratory adaptations to treadmill training, and such impairments would be exacerbated with statin treatment. Adult ApoE−/− mice with genetically high cholesterol were divided into 4 groups (n= 5–6/group) and completed 14d of treadmill training (60 min/day) or remained sedentary while receiving daily placebo or atorvastatin. Cardiorespiratory adaptations were assessed by pre‐ and post‐maximal treadmill tests. After 14d, muscle function was analyzed in vivo by measuring strength and fatigability (% of maximal force after 10 contractions) with a dual mode footplate system. Data were analyzed with 2‐way ANOVAs and post‐hoc tests. After testing, hindlimb muscles and hearts were harvested and frozen for Elisa assays to quantify IL‐6 and vascular endothelial growth factor (VEGF). Atorvastatin was associated with decreased maximal isometric force relative to body or gastrocnemius mass in both sedentary and treadmill groups (1.44±0.10 vs. 1.15±0.16 and 1.51±0.07 vs. 1.22±0.21 g/g body mass, respectively, p<0.05). Muscle fatigability was similar among all conditions; average group values ranged from 33%‐34% of maximum. Cardiorespiratory fitness increased in both treadmill groups with 12:17±6:36 and 12:56±4:23 min increases in maximal test time for placebo and statin groups, respectively (p<0.05). Maximal test time was unchanged in sedentary groups. Treadmill training decreased respective muscle IL‐6 and VEGF levels by 87 and 64% and 50 and 45% compared to sedentary, in placebo and statin groups, respectively (p<0.05). Treadmill training decreased heart IL‐6 32 and 50% compared to sedentary, in placebo and statin groups, respectively (p<0.05). Training decreased heart VEGF 41% in placebo group only (p<0.05). These findings suggest statin treatment impairs muscle strength in both sedentary and treadmill‐trained hypercholesterolemic mice, but does not alter muscle fatigue or cardiorespiratory adaptations to exercise training. Additionally, statins did not affect training‐associated reductions in the inflammatory cytokine, IL‐6. Further research is needed to determine biological and/or cellular mechanisms whereby statin medications affect muscular strength independent of muscular and cardiorespiratory endurance.Support or Funding InformationAPS STRIDE Fellowship Program and Grant #1 R25 HL115473‐01This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.