Modulating the Vascular Response to Limb Ischemia: Angiogenic and Cell Therapies

John P. Cooke, Douglas W. Losordo

Research output: Contribution to journalArticlepeer-review

149 Scopus citations


The age-adjusted prevalence of peripheral arterial disease in the US population has been estimated to approach 12%. The clinical consequences of occlusive peripheral arterial disease include pain on walking (claudication), pain at rest, and loss of tissue integrity in the distal limbs; the latter may ultimately lead to amputation of a portion of the lower extremity. Surgical bypass techniques and percutaneous catheter-based interventions may successfully reperfuse the limbs of certain patients with peripheral arterial disease. In many patients, however, the anatomic extent and distribution of arterial occlusion is too severe to permit relief of pain and healing of ischemic ulcers. No effective medical therapy is available for the treatment of such patients, for many of whom amputation represents the only hope for alleviation of symptoms. The ultimate failure of medical treatment and procedural revascularization in significant numbers of patients has led to attempts to develop alternative therapies for ischemic disease. These strategies include administration of angiogenic cytokines, either as recombinant protein or as gene therapy, and more recently, to investigations of stem/progenitor cell therapy. The purpose of this review is to provide an outline of the preclinical basis for angiogenic and stem cell therapies, review the clinical research that has been done, summarize the lessons learned, identify gaps in knowledge, and suggest a course toward successfully addressing an unmet medical need in a large and growing patient population.

Original languageEnglish (US)
Pages (from-to)1561-1578
Number of pages18
JournalCirculation Research
Issue number9
StatePublished - Apr 24 2015


  • angiogenesis
  • genetic therapy
  • microvessels
  • progenitor cell
  • stem cells
  • vasculogenesis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine


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