Abstract 501: Irregular Distribution and Accumulation of Desmin in Gastrocnemius Myofibers in Association With Abnormal Myofiber Morphology and Impaired Limb Function in a Mouse Model of Chronic, Hindlimb Ischemia
A myopathy characterized by myofiber degeneration and impaired limb function is present in the legs of patients with peripheral artery disease (PAD). A characteristic of myofibers in PAD legs is abnormal distribution and accumulation of desmin, a key protein of the myofiber cytoskeleton. Using a mouse model of chronic hindlimb ischemia, we investigated the effects of chronic inflow arterial occlusion on myofiber morphology and desmin expression in the gastrocnemius, in relation to limb function. Hindlimb ischemia was induced by staged ligation/division of the common femoral and iliac arteries of C57BL/6 mice and muscles were harvested 12 weeks later. Desmin expression was analyzed by quantitative fluorescence microscopy of slide-mounted gastrocnemius specimens and by Western Blot analysis of gastrocnemius lysates of 10 ischemic and 10 control mice. Gastrocnemius myofiber morphometrics were determined by fluorescence microscopy and limb muscle endurance was measured with a RotaRod apparatus. Desmin was significantly increased both in myofibers and in lysates of ischemic muscle compared to control muscle (+35%, p<0.001; +79%, p<0.01 respectively). Increased abundance was associated with a loss of organization of the protein, indicating damage to the cytoskeleton of the ischemic myofibers. These changes in desmin correlated with decreased cross-sectional area and solidity and increased roundness of the myofibers (p<0.01) and reduced limb muscle endurance (p <0.01). Using a mouse model of hindlimb ischemia, we have demonstrated that inflow arterial occlusion, produces a myopathy with abnormal distribution and accumulation of desmin, abnormal myofiber morphology and reduced limb muscle endurance, recapitulating the muscle pathology of PAD patients.
Author Disclosures: P. Koutakis: Research Grant; Significant; American Heart Association Pre-Doctoral Fellowship, Midwest Affiliate (13PRE13860010). S.A. Swanson: None. Z. Zhu: None. E. Papoutsi: None. D. Miserlis: None. J. Kim: None. I.I. Pipinos: None. G.P. Casale: None.
- © 2015 by American Heart Association, Inc.