Blood and Nerve

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Science  08 Jun 2001:
Vol. 292, Issue 5523, pp. 1799-1801
DOI: 10.1126/science.292.5523.1799e

Vascular endothelial growth factor (VEGF) plays a key role in controlling the growth and permeability of blood vessels. When oxygen levels fall (hypoxia), VEGF is rapidly up-regulated, thereby ensuring that tissues are perfused adequately, through a promoter sequence in the VEGF gene called the hypoxia response element (HRE). Oosthuyse et al. generated mice that were lacking the HRE and therefore produced inadequate amounts of VEGF under hypoxic conditions. Surprisingly, the mice developed an adult-onset neurodegenerative disease with many of the characteristics of amyotrophic lateral sclerosis (Lou Gehrig's disease). The motor neuron degeneration in the mice appeared to be caused in part by a reduction in neural vascular perfusion, but cell culture studies supported the tantalizing possibility that VEGF served as a survival factor for motor neurons.

This connection to neuronal ischemia also was noted by Schratzberger et al. in a recent study of diabetic neuropathy, a frequent complication of diabetes in which patients experience loss of sensation in their lower extremities. Intramuscular injection of VEGF DNA in two animal models of diabetic neuropathy resulted in restoration of peripheral nerve function, and this reversal of symptoms correlated with an increase in nerve blood flow. Together, these studies raise the possibility that VEGF may have therapeutic applications well beyond those originally envisaged. — PAK

Nature Genet. 28, 131 (2001); J. Clin. Invest. 107, 1083 (2001).

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