Skeletal Muscle Pathology in Peripheral Artery Disease: A Brief Review

Mary M. McDermott, Luigi Ferrucci, Marta Gonzalez-Freire, Kate Kosmac, Christiaan Leeuwenburgh, Charlotte A. Peterson, Sunil Saini, Robert Sufit

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


This brief review summarizes current evidence regarding lower extremity peripheral artery disease (PAD) and lower extremity skeletal muscle pathology. Lower extremity ischemia is associated with reduced calf skeletal muscle area and increased calf muscle fat infiltration and fibrosis on computed tomography or magnetic resonance imaging. Even within the same individual, the leg with more severe ischemia has more adverse calf muscle characteristics than the leg with less severe ischemia. More adverse computed tomography-measured calf muscle characteristics, such as reduced calf muscle density, are associated with higher rates of mobility loss in people with PAD. Calf muscle in people with PAD may also have reduced mitochondrial activity compared with those without PAD, although evidence is inconsistent. Muscle biopsy document increased oxidative stress in PAD. Reduced calf muscle perfusion, impaired mitochondrial activity, and smaller myofibers are associated with greater walking impairment in PAD. Preliminary evidence suggests that calf muscle pathology in PAD may be reversible. In a small uncontrolled trial, revascularization improved both the ankle-brachial index and mitochondrial activity, measured by calf muscle phosphocreatine recovery time. A pilot clinical trial showed that cocoa flavanols increased measures of myofiber health, mitochondrial activity, and capillary density while simultaneously improving 6-minute walk distance in PAD. Calf muscle pathological changes are associated with impaired walking performance in people with PAD, and interventions that both increase calf perfusion and improve calf muscle health are promising therapies to improve walking performance in PAD. Graphic Abstract: A graphic abstract is available for this article.

Original languageEnglish
Pages (from-to)2577-2585
Number of pages9
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number11
StatePublished - Nov 1 2020

Bibliographical note

Publisher Copyright:
© 2020 Lippincott Williams and Wilkins. All rights reserved.


  • ischemia
  • mitochondria
  • muscles
  • peripheral artery disease
  • reperfusion injury

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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