title: Oxidative damage in the gastrocnemius of patients with peripheral artery disease is myofiber type selective.
abstract: BACKGROUND
  Peripheral artery disease (PAD), a manifestation of systemic atherosclerosis that produces blockages in the arteries supplying the legs, affects approximately 5% of Americans. We have previously, demonstrated that a myopathy characterized by myofiber oxidative damage and degeneration is central to PAD pathophysiology.
  
  
  OBJECTIVE
  In this study, we hypothesized that increased oxidative damage in the myofibers of the gastrocnemius of PAD patients is myofiber-type selective and correlates with reduced myofiber size.
  
  
  METHODS
  Needle biopsies were taken from the gastrocnemius of 53 PAD patients (28 with early PAD and 25 with advanced PAD) and 25 controls. Carbonyl groups (marker of oxidative damage), were quantified in myofibers of slide-mounted tissue, by quantitative fluorescence microscopy. Myofiber cross-sectional area was determined from sarcolemma labeled with wheat germ agglutinin. The tissues were also labeled for myosin I and II, permitting quantification of oxidative damage to and relative frequency of the different myofiber Types (Type I, Type II and mixed Type I/II myofibers). We compared PAD patients in early (N=28) vs. advanced (N=25) disease stage for selective, myofiber oxidative damage and altered morphometrics.
  
  
  RESULTS
  The carbonyl content of gastrocnemius myofibers was higher in PAD patients compared to control subjects, for all three myofiber types (p<0.05). In PAD patients carbonyl content was higher (p<0.05) in Type II and I/II fibers compared to Type I fibers. Furthermore, the relative frequency and cross-sectional area of Type II fibers were lower, while the relative frequencies and cross-sectional area of Type I and Type I/II fibers were higher, in PAD compared to control gastrocnemius (p<0.05). Lastly, the type II-selective oxidative damage increased and myofiber size decreased as the disease progressed from the early to advanced stage.
  
  
  CONCLUSIONS
  Our data confirm increased myofiber oxidative damage and reduced myofiber size in PAD gastrocnemius and demonstrate that the damage is selective for type II myofibers and is worse in the most advanced stage of PAD.
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, United States.
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Koutakis
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, United States.
authors.forename: Dustin J
authors.initials: DJ
authors.lastname: Weiss
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, United States.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Miserlis
authors.affiliation: Department of Biostatistics, University of Nebraska Medical Center, Omaha, NE, United States.
authors.forename: Valerie K
authors.initials: VK
authors.lastname: Shostrom
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, United States.
authors.forename: Evlampia
authors.initials: E
authors.lastname: Papoutsi
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, United States.
authors.forename: Duy M
authors.initials: DM
authors.lastname: Ha
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, United States.
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Carpenter
authors.affiliation: Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE, United States.
authors.forename: Rodney D
authors.initials: RD
authors.lastname: McComb
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, United States.
authors.forename: George P
authors.initials: GP
authors.lastname: Casale
authors.affiliation: Department of Surgery, University of Nebraska Medical Center, Omaha, NE, United States ; Department of Surgery and VA Research Service, VA Nebraska-Western Iowa Health Care System, Omaha, NE, United States.
authors.forename: Iraklis I
authors.initials: II
authors.lastname: Pipinos
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018485:Muscle Fibers, Skeletal / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress; D058729:Peripheral Arterial Disease / Q000378:metabolism* / Q000473:pathology*
keywords: Fontaine Stage; carbonyl groups; oxidative damage