Schmidt 2017 J Vasc Surg

From Bioblast
Publications in the MiPMap
Schmidt CA, Ryan TE, Lin CT, Inigo MM, Green TD, Brault JJ, Spangenburg EE, McClung JM (2017) Diminished force production and mitochondrial respiratory deficits are strain-dependent myopathies of subacute limb ischemia. J Vasc Surg 65:1504-1514.

Β» PMID: 28024849 Open Access

Schmidt CA, Ryan TE, Lin CT, Inigo MM, Green TD, Brault JJ, Spangenburg EE, McClung JM (2017) J Vasc Surg

Abstract: Reduced skeletal muscle mitochondrial function might be a contributing mechanism to the myopathy and activity based limitations that typically plague patients with peripheral arterial disease (PAD). We hypothesized that mitochondrial dysfunction, myofiber atrophy, and muscle contractile deficits are inherently determined by the genetic background of regenerating ischemic mouse skeletal muscle, similar to how patient genetics affect the distribution of disease severity with clinical PAD.

Genetically ischemia protected (C57BL/6) and susceptible (BALB/c) mice underwent either unilateral subacute hind limb ischemia (SLI) or myotoxic injury (cardiotoxin) for 28 days. Limbs were monitored for blood flow and tissue oxygen saturation and tissue was collected for the assessment of histology, muscle contractile force, gene expression, mitochondrial content, and respiratory function.

Despite similar tissue O2 saturation and mitochondrial content between strains, BALB/c mice suffered persistent ischemic myofiber atrophy (55.3% of C57BL/6) and muscle contractile deficits (approximately 25% of C57BL/6 across multiple stimulation frequencies). SLI also reduced BALB/c mitochondrial respiratory capacity, assessed in either isolated mitochondria (58.3% of C57BL/6 at SLI on day (d)7, 59.1% of C57BL/6 at SLI d28 across multiple conditions) or permeabilized myofibers (38.9% of C57BL/6 at SLI d7; 76.2% of C57BL/6 at SLI d28 across multiple conditions). SLI also resulted in decreased calcium retention capacity (56.0% of C57BL/6) in BALB/c mitochondria. Nonischemic cardiotoxin injury revealed similar recovery of myofiber area, contractile force, mitochondrial respiratory capacity, and calcium retention between strains.

Ischemia-susceptible BALB/c mice suffered persistent muscle atrophy, impaired muscle function, and mitochondrial respiratory deficits during SLI. Interestingly, parental strain susceptibility to myopathy appears specific to regenerative insults including an ischemic component. Our findings indicate that the functional deficits that plague PAD patients could include mitochondrial respiratory deficits genetically inherent to the regenerating muscle myofibers.

Copyright Β© 2016 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

β€’ Bioblast editor: Kandolf G β€’ O2k-Network Lab: US NC Greenville Neufer PD

Labels: MiParea: Respiration  Pathology: Myopathy, Other  Stress:Hypoxia  Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue, Isolated mitochondria  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase  Regulation: Calcium  Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS  HRR: Oxygraph-2k 

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