Endothelial interleukin-21 receptor up-regulation in peripheral artery disease

Tao Wang, Alexis Cunningham, Kevin Houston, Aditya M. Sharma, Lingdan Chen, Ayotunde O. Dokun, R. John Lye, Rosanne Spolski, Warren J. Leonard, Brian H. Annex

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


In most patients with symptomatic peripheral artery disease (PAD), severe stenosis in or occlusion of the major blood vessels that supply the legs make the amount of distal blood flow dependent on the capacity to induce angiogenesis and collateral vessel formation. Currently, there are no medications that improve perfusion to the ischemic limb, and thus directly treat the primary problem of PAD. A recent report from our group in a pre-clinical mouse PAD model showed that interleukin-21 receptor (IL-21R) is up-regulated in the endothelial cells from ischemic hindlimb muscle. We further showed that loss of IL-21R resulted in impaired perfusion recovery in this model. In our study, we sought to determine whether IL-21R is present in the endothelium from ischemic muscle of patients with PAD. Using human gastrocnemius muscle biopsies, we found increased levels of IL-21R in the skeletal muscle endothelial cells of patients with PAD compared to control individuals. Interestingly, PAD patients had approximately 1.7-fold higher levels of circulating IL-21. These data provide direct evidence that the IL-21R pathway is indeed up-regulated in patients with PAD. This pathway may serve as a therapeutic target for modulation.

Original languageEnglish (US)
Pages (from-to)99-104
Number of pages6
JournalVascular Medicine (United Kingdom)
Issue number2
StatePublished - Apr 1 2016
Externally publishedYes


  • IL-2R
  • PAD
  • endothelial cells
  • interleukin-21 receptor
  • ischemia
  • peripheral artery disease

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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