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Ryan 2016 J Mol Cell Cardiol

From Bioblast
Publications in the MiPMap
Ryan TE, Schmidt CA, Alleman RJ, Tsang AM, Green TD, Neufer PD, Brown DA, McClung JM (2016) Mitochondrial therapy improves limb perfusion and myopathy following hindlimb ischemia. J Mol Cell Cardiol 97:191-6.

ยป PMID: 27262673

Ryan TE, Schmidt CA, Alleman RJ, Tsang AM, Green TD, Neufer PD, Brown DA, McClung JM (2016) J Mol Cell Cardiol

Abstract: Critical limb ischemia is a devastating manifestation of peripheral arterial disease with no effective strategies for improving morbidity and mortality outcomes. We tested the hypothesis that cellular mitochondrial function is a key component of limb pathology and that improving mitochondrial function represents a novel paradigm for therapy. BALB/c mice were treated with a therapeutic mitochondrial-targeting peptide (MTP-131) and subjected to limb ischemia (HLI). Compared to vehicle control, MTP-131 rescued limb muscle capillary density and blood flow (64.7ยฑ11% of contralateral vs. 39.9ยฑ4%), and improved muscle regeneration. MTP-131 also increased electron transport system flux across all conditions at HLI day-7. In vitro, primary muscle cells exposed to experimental ischemia demonstrated markedly reduced (~75%) cellular respiration, which was rescued by MTP-131 during a recovery period. Compared to muscle cells, endothelial cell (HUVEC) respiration was inherently protected from ischemia (~30% reduction), but was also enhanced by MTP-131. These findings demonstrate an important link between ischemic tissue bioenergetics and limb blood flow and indicate that the mitochondria may be a pharmaceutical target for therapeutic intervention during critical limb ischemia.

Copyright ยฉ 2016. Published by Elsevier Ltd. โ€ข Keywords: Critical limb ischemia, Ischemia, Mitochondria, Peripheral artery disease

โ€ข O2k-Network Lab: US NC Greenville Neufer PD, US NC Greenville Brown DA, US VA Blacksburg Brown DA

Labels: MiParea: Respiration, mt-Medicine 

Stress:Ischemia-reperfusion  Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS, ET  Pathway: N, S, CIV, NS, ROX  HRR: Oxygraph-2k