Abstract 15850: Desmin Expression is Abnormal in Myofibers of the Gastrocnemius of Patients With Peripheral Arterial Disease and is Associated With Impaired Mitochondrial Respiration and Reduced Muscle Strength

Introduction: Patients with peripheral arterial disease (PAD) develop a myopathy in their ischemic limbs which is characterized by myofiber degeneration, mitochondrial dysfunction and decreased muscle force production. Desmin, a cytoskeletal protein of the myofiber, is central to maintenance of the structure, shape and function of the myofiber and its organelles especially the mitochondria. Hypothesis: We hypothesized that desmin expression in myofibers of the gastrocnemius of PAD patients is abnormal and correlates with decreased mitochondrial respiration and reduced muscle strength. Methods and Results: We quantified desmin protein and gene transcripts in myofibers of gastrocnemius biopsies from 30 PAD patients and 29 controls and determined their association with myofiber morphology, mitochondrial respiration and calf muscle strength. Compared to control, desmin protein and gene transcripts were increased in myofibers of PAD gastrocnemius. Increased expression was associated with a diffuse appearance of the protein, suggesting a loss of its normally filamentous structure. These changes in desmin correlated with altered myofiber morphology, decreased mitochondrial respiration and reduced calf muscle strength. Conclusions: Desmin expression and organization are abnormal in myofibers of the gastrocnemius of patients with PAD and these changes correlate with decreased mitochondrial function and reduced muscle strength.