Endogenous vascular endothelial growth factor and angiopoietin-2 expression in critical limb ischemia

The aim of this paper was to contribute to a better understanding of the angiogenesis in peripheral arterial disease (PAD); we evaluated the expression of vascular endothelial growth factor (vegf) and angiopoietin-2 (Ang-2) in critical limb ischemia (CLI).

Skin and muscle biopsies were collected from 12 patients submitted to major amputation for CLI, proximal samples from amputation level and distal ones from the more ischemic region. Three controls were obtained from orthopedic patients. Capillary density was determined in random selected high-power fields. Expression pattern of VEGF and Ang-2 was studied by immunohistochemistry and quantification was performed by enzyme-linked immunosorbent assay.

In skin, capillary density and levels of VEGF and Ang-2 were higher in distal samples when compared to proximal (capillary density, P=0.003, VEGF, P=0.008, Ang-2, P=0.041). Distal muscle had also elevated capillary number (P=0.005) and Ang-2 concentration (P=0.023). VEGF concentration in distal muscle was found to be similar to proximal muscle (P=1). Immunohistochemical expression of VEGF was clearly more evident in distal samples and was predominantly present in epidermis and skeletal myocytes. Ang-2 was essentially detected distally and only observed in endothelial cells.

The capillary density is enhanced in distal samples, suggesting an effective angiogenic drive in CLI. In addition, the observed increase of VEGF expression in ischemic skin and Ang-2 in ischemic skin and muscle may contribute to clarify the potential role of VEGF and Ang-2 supplementation for therapeutic angiogenesis in CLI.