Limb ischemia and vessel regeneration: Is there a role for VEGF?

Vascular endothelial growth factor (VEGF), as an endothelial cell-specific mitogen, is crucial for new blood vessels formation. Atherosclerosis affecting the cardiovascular system causes ischemia and functio laesa in tissues supplied by the occluded vessels. When such a situation occurs in the lower extremities, it causes critical limb ischemia (CLI) often requiring leg amputation. Low oxygen tension leads to upregulation of hypoxia-regulated genes (i.e. VEGF), that should help to restore the impaired blood flow. In CLI these rescue mechanisms are, however, often inefficient. Moreover, there are many contradictory reports showing either induction, no changes or even down-regulation of VEGF in specimens taken from patients with CLI, as well as in samples collected from animals subjected to hindlimb ischemia. Additionally, taking into account numerous experimental and clinical data demonstrating rather insufficient therapeutic potential of VEGF, we called into question the role of this protein in limb ischemia and vessel regeneration. In this review we are also summarizing several aspects which can influence VEGF expression and its measurement in the ischemic tissues.