Peripheral artery disease (PAD) is the third leading cause of atherosclerotic cardiovascular mortality, with an estimated age-adjusted prevalence of at least 12% in the United States. Critical limb ischemia (CLI) is the most severe form of peripheral arterial disease (PAD), and carries a substantially high morbidity and mortality rate. Further, CLI patients have a risk of major amputation or death that approaches 40% in the first year of diagnosis.
Dr. Joseph McClung from the Department of Physiology has discovered that mitochondrial mechanisms by which limb muscle cells respond to ischemia and influence the limb vasculature in PAD may represent a new strategy to prevent tissue loss and subsequent limb amputation in patients with CLI. Specifically, modulation of oxidiative and/or glycolytic metabolism by delivery of Cox6a2 to ischemic muscle tissue may hold the key to improving limb muscle mitochondrial respiration and protecting the vascular network. Preliminary data in a mouse model of ischemia demonstrates that Cox6a2 protein abundance is in-part required for protection from ischemic mitochondriopathy and therapeutic re-expression is sufficient to alleviate ischemic pathology. Further, re-expression of Cox6a2 during ischemia rescues mitochondriopathy and regenerative myopathy in CLI In human primary muscle cells.