Angiogenesis in skeletal muscle precede improvements in peak oxygen uptake in peripheral artery disease patients

Brian D. Duscha, Jennifer L. Robbins, William S. Jones, William E. Kraus, R. John Lye, John M. Sanders, Jason D. Allen, Judith G. Regensteiner, William R. Hiatt, Brian H. Annex

Research output: Contribution to journalArticlepeer-review

92 Scopus citations


Objective-: Peripheral artery disease (PAD) is characterized by impaired blood flow to the lower extremities, causing claudication and exercise intolerance. The mechanism(s) by which exercise training improves functional capacity is not understood. This study tested the hypothesis that in PAD patients who undergo supervised exercise training, increases in capillary density (CD) in calf muscle take place before improvements in peak oxygen uptake (VO 2). Methods and Results-: Thirty-five PAD patients were randomly assigned to 12 weeks of directly supervised or home-based exercise training. Peak VO 2 testing and gastrocnemius muscle biopsies were performed at baseline and after training. CD (endothelial cells/mm) was measured using immunofluorescence staining. After 3 weeks of directly supervised training, patients had an increase in CD (216±66 versus 284±77, P<0.01) but no increase in peak VO 2. However, after 12 weeks, peak VO 2 increased (15.3±2.8 versus 16.8±3.8, P<0.01), whereas in muscle, CD remained increased over baseline, but there were no changes in markers of oxidative capacity. Within subjects, CD was related to peak VO 2 before and after directly supervised training. Conclusion-: Changes in CD in ischemic muscle with training may modulate the response to training, and those changes precede the increase in VO 2.

Original languageEnglish (US)
Pages (from-to)2742-2748
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Issue number11
StatePublished - Nov 2011
Externally publishedYes


  • angiogenesis
  • exercise
  • peripheral arterial disease

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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