Abstract 19234: Revascularization Improves the Levels and Organization of the Desmin Cytoskeletal System in the Gastrocnemius of Patients With Peripheral Artery Disease
Introduction: Patients with peripheral artery disease (PAD) develop a myopathy in their ischemic limbs which is characterized by myofiber degeneration, mitochondrial dysfunction and impaired leg function. Degenerated myofibers have cytoskeletal abnormalities the best described of which is a disorganized accumulation of desmin filaments. The degree of disruption of the desmin system has been associated with altered myofiber morphology, decreased mitochondrial respiration, reduced calf muscle strength and decreased walking performance.
Hypothesis: We hypothesized that the levels and organization of desmin in the myofibers of the gastrocnemius of PAD patients improve after revascularization and correlate with increases in mitochondrial respiration and calf muscle strength.
Methods: Gastrocnemius biopsies were collected from 32 PAD patients, before and six months after revascularization. Accumulation and organization of desmin protein in myofibers were determined by quantitative fluorescence microscopy and desmin gene transcripts were quantified by rtPCR of RNA in biopsy homogenates. We evaluated the effects of revascularization on these parameters and their association with ischemic window (a measure of lower limb hemodynamic limitation), mitochondrial function determined by respirometry, and calf muscle strength.
Results: Revascularization reduced the abnormal accumulation of disorganized desmin protein and gene transcripts in the PAD gastrocnemius. The ischemic window, myofiber morphology, mitochondrial respiration and calf muscle strength were significantly improved after revascularization. After revascularization, the decreased desmin expression was associated with a more structured appearance of the protein, suggesting a return to the normally filamentous structure. These changes in desmin correlated with improved mitochondrial function and increased calf muscle strength.
Conclusions: Revascularization operations improve the levels and organization of the desmin filaments in the gastrocnemius of patients with PAD and these changes correlate with improved mitochondrial function and calf muscle strength.
Author Disclosures: P. Koutakis: Research Grant; Significant; American Heart Association Post-Doctoral Fellowship 15POST25520004. G.P. Casale: None. E. Papoutsi: None. J. Kim: None. D. Miserlis: None. G. Haynatzki: None. H.K. DeSpiegelaere: None. H. Hernandez: None. C.J. Mietus: None. D.M. Ha: None. P. Karvelis: None. Z. Zhu: None. N. Tsigkas: None. Y.S. Chatzizisis: None. I.I. Pipinos: None.
- © 2016 by American Heart Association, Inc.