Mitochondrial Therapy Improves Limb Perfusion and Myopathy Following Hindlimb Ischemia

Overview

Journal J Mol Cell Cardiol

Specialty Cardiology & Vascular Diseases

Date 2016 Jun 6

PMID 27262673

Citations 23

Authors

Terence E Ryan

Cameron A Schmidt

Rick J Alleman

Alvin M Tsang

Thomas D Green

P Darrell Neufer

David A Brown

Joseph M McClung

Affiliations

Soon will be listed here.

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 (64.7±11% of contralateral vs. 39.9±4%), 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.

Citing Articles

A 6-Minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models.

Palzkill V, Tan J, Moparthy D, Tice A, Ferreira L, Ryan T JACC Basic Transl Sci. 2025; 10(1):88-103.

PMID: 39906594 PMC: 11788496. DOI: 10.1016/j.jacbts.2024.08.011.

A 6-minute Limb Function Assessment for Therapeutic Testing in Experimental Peripheral Artery Disease Models.

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IGF-1 Therapy Improves Muscle Size and Function in Experimental Peripheral Arterial Disease.

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