Acquired skeletal muscle metabolic myopathy in atherosclerotic peripheral arterial disease

Peripheral arterial disease (PAD) is associated with an increased risk of o verall cardiovascular mortality, and substantial morbidity resulting from c laudication, While the initial disease process is clearly the result of ath erosclerosis in the arterial circulation of the limb, altered hemodynamics do not completely explain the pathophysiology of claudication. Work from se veral laboratories has demonstrated secondary changes in the skeletal muscl e of patients with PAD which are consistent with the presence of an acquire d metabolic myopathy in these patients. Key findings include an alteration in the expression df mitochondrial enzymes, the accumulation of metabolic i ntermediates, altered regulation of mitochondrial respiration, increased ox idative stress, and the presence of somatic mutations in the mitochondrial genome. Understanding the metabolic changes associated with PAD is importan t in understanding the pathophysiology of claudication and in the developme nt of novel therapeutic strategies.