Chronically ischemic mouse skeletal muscle exhibits myopathy in association with mitochondrial dysfunction and oxidative damage

Abstract

Pipinos II, Swanson SA, Zhu Z, Nella AA, Weiss DJ, Gutti TL, McComb RD, Baxter BT, Lynch TG, Casale GP. Chronically ischemic mouse skeletal muscle exhibits myopathy in association with mitochondrial dysfunction and oxidative damage.

Investigation of the Oxidative Stress, the Altered Function of Platelets and Neutrophils, in thePatients with Peripheral Arterial Disease

“…It has to be mentioned that SOD deficiency is a highly important determinant of the increased ROS production and the increase in platelet aggregation one week after the surgery. Pipinos and co-workers published that, the SOD enzyme mutation of gastrocnemius muscle of rats is a risk factor of PAD, (Pipinos II and Swanson SA 2008). Intracellular GSH and the plasma -SH groups possess remarkable antioxidant capacities.…”

Skeletal Muscle Mitochondrial Function in Peripheral Arterial Disease: Usefulness of Muscle Biopsy

“…Peripheral arterial disease is a consequence of compromised blood supply to the ischemic limb (Brass, 1996;Brass & Hiatt, 2000). Experimental data show that skeletal muscle responds to inflow arterial occlusion with the development of myopathic histological changes, a drop in total protein content, and a trend toward decreased wet weight (Makris, et al, 2007 ;Pipinos, et al, 2008b). Peripheral arterial disease is characterized by a significant increase in the mitochondrial content of skeletal muscle, and mitochondrial proliferation is characteristic of mitochondrial diseases and aging (Levak-Frank et al, 1995;Wallace, 2000;Wredenberg et al, 2002;Makris et al, 2007;Pipinos et al, 2008b).…”

“…Experimental data show that skeletal muscle responds to inflow arterial occlusion with the development of myopathic histological changes, a drop in total protein content, and a trend toward decreased wet weight (Makris, et al, 2007 ;Pipinos, et al, 2008b). Peripheral arterial disease is characterized by a significant increase in the mitochondrial content of skeletal muscle, and mitochondrial proliferation is characteristic of mitochondrial diseases and aging (Levak-Frank et al, 1995;Wallace, 2000;Wredenberg et al, 2002;Makris et al, 2007;Pipinos et al, 2008b). In skeletal muscle, an upregulation of mitochondrial biogenesis may be associated with and alteration of muscle fibre type toward the more oxidative type I and IIa fibres (Pipinos et al, 2008b).…”

“…Thus, PAD myopathy is characterized by an increased content of dysfunctional mitochondria having significant defects in electron transport chain complexes I, III, and IV (Pipinos et al, 2000;Pipinos et al, 2008b). These defects are associated with a bioenergetic decline, characterized by inadequate oxidative phosphorylation, decreased ATP energy production, and increased oxidative stress (Makris et al, 2007;Pipinos et al, 2008b).…”

“…Contraindications are essentially represented by bleeding disorders, infection at biopsy sites, or allergy to local anesthetics. Previous studies have shown that PAD is associated with alterations in skeletal muscle histology (Brass & Hiatt, 2000;Makris et al, 2007;Pipinos et al, 2008b). Necrotic and r e g e n e r a t i n g f i b r e s a s w e l l a s i n f l a m m a t i o n h a v e b e e n s e e n i n t h e d i s e a s e d l e g s i n comparison to contralateral legs of patients with unilateral peripheral arterial disease hospitalized for surgical evaluation.…”