Training monocytes by physical exercise: good practice for improving collateral artery development and postischemic outcomes.

Abstract

Peripheral artery disease is caused by obstructing atherosclerotic plaques that critically reduce blood flow during exercise. The disease affects ≈4% of people >40 years and 15% to 20% of subjects above 65 years of age. Critical limb ischemia, the most severe manifestation of peripheral artery disease, describes patients with chronic ischemic rest pain, or patients with ischemic skin lesions, either ulcers or gangrene. It requires foot amputation in 25% of cases within 1 year from the diagnosis. Revascularization therapies are indicated in critical limb ischemia patients, but they are often ineffective or unfeasible; and in the latter case, the reported amputation and mortality rates exceed 50%. Therefore, new therapeutic approaches are urgently needed. See accompanying article on page 1862 Promotion of arteriogenesis, which refers to the enlargement and functionalization of preformed collateral arterioles, represents a promising therapeutic approach in critical limb ischemia patients. Several clinical studies have used the administration of growth factors (mostly basic fibroblast growth factor or vascular endothelial growth factor, either as protein or gene therapy) or stem and progenitor cells.1 In addition, exercise rehabilitation programs have been shown to improve symptoms of claudication.2,3 Mechanistic understanding of how physical exercise increases collateral artery formation is inadequate. The new study from Schirmer et al4 shows that voluntary training confers mice with an …