Exercise-induced VEGF transcriptional activation in brain, lung and skeletal muscle.

Muscle VEGF expression is upregulated by exercise. Whether this VEGF response is regulated by transcription and/or post-transcriptional mechanisms is unknown. Hypoxia may be responsible: myocyte P(O2) falls greatly during exercise and VEGF is a hypoxia-responsive gene. Whether exercise induces VEGF expression in other organs important to acute physical activity is also unknown. To address these questions, we created a VEGF-Luciferase reporter mouse and measured VEGF transcription, mRNA and protein responses to (a) acute exercise and (b) short-term hypoxia (FI(O2) = 0.06) in brain (brainstem, cerebellum, cortex, hippocampus and striatum), muscle, lung, heart and liver. Exercise increased VEGF transcription, mRNA and protein in brain (hippocampus only), lungs and skeletal muscles, but not liver or heart. Hypoxia increased VEGF expression only in brain (cortex, hippocampus and striatum). New transcription appears to be a major exercise-induced regulatory step for increasing VEGF expression in muscle, lung and brain. Hippocampal VEGF expression was the only component of the exercise response recapitulated by hypoxia equivalent to the Everest summit.