Abstract
Exercise training (ET) is recommended for lower extremity artery disease (LEAD) management. However, there is still little information on the hemodynamic and metabolic adaptations by skeletal muscle with ET. We examined whether hindlimb perfusion/vascularization and muscle energy metabolism are altered differently by three types of aerobic ET. ApoE−/− mice with LEAD were assigned to one of four groups for 4 weeks: sedentary (SED), forced treadmill running (FTR), voluntary wheel running (VWR), or forced swimming (FS). Voluntary exercise capacity was improved and equally as efficient with FTR and VWR, but remained unchanged with FS. Neither ischemic hindlimb perfusion and oxygenation, nor arteriolar density and mRNA expression of arteriogenic-related genes differed between groups. 18FDG PET imaging revealed no difference in the steady-state levels of phosphorylated 18FDG in ischemic and non-ischemic hindlimb muscle between groups, nor was glycogen content or mRNA and protein expression of glucose metabolism-related genes in ischemic muscle modified. mRNA (but not protein) expression of lipid metabolism-related genes was upregulated across all exercise groups, particularly by non-ischemic muscle. Markers of mitochondrial content (mitochondrial DNA content and citrate synthase activity) as well as mRNA expression of mitochondrial biogenesis-related genes in muscle were not increased with ET. Contrary to FTR and VWR, swimming was ineffective in improving voluntary exercise capacity. The underlying hindlimb hemodynamics or muscle energy metabolism are unable to explain the benefits of running exercise.
Highlights
Exercise training (ET) is recommended for lower extremity artery disease (LEAD) management
ApoE−/− mice underwent right iliac artery ligation, and at one week post-surgery, they were randomized into four groups for the reminder of the 5 weeks study: sedentary (SED), forced treadmill running (FTR), voluntary wheel running (VWR), or forced swimming (FS), as detailed in “Methods”
Since glucose metabolism is influenced by glucose transporters (GLUT-1, GLUT-4) and key regulatory enzymes in glycolysis, e.g. hexokinase (HK), phosphofructose kinase (PFK), and pyruvate dehydrogenase kinase (PDK), we examined their corresponding mRNA expression in non-ischemic and ischemic hindlimb muscle (Fig. 4A)
Summary
Exercise training (ET) is recommended for lower extremity artery disease (LEAD) management. Voluntary exercise capacity was improved and as efficient with FTR and VWR, but remained unchanged with FS. MRNA (but not protein) expression of lipid metabolism-related genes was upregulated across all exercise groups, by non-ischemic muscle. Contrary to FTR and VWR, swimming was ineffective in improving voluntary exercise capacity. According to current international guidelines, the first-line conservative treatment modality for improving walking capacity in IC patients consists in pharmacotherapy and exercise training (ET)[2,3]. The efficiency of ET in improving walking capacity has been widely demonstrated in IC patients, the underlying mechanisms remain incompletely understood. There is still little experimental evidence demonstrating such ET-mediated adaptations in LEAD It remains unknown whether ET type affects those mechanisms differently
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