The Role Of PO2, HbO2 and Exercise in Human VEGF mRNA Expression

Abstract

0392 Oxygen availability may regulate skeletal muscle gene transcription of vascular endothelial growth factor (VEGF), a major angiogenic growth factor. PURPOSE: As hypoxia (H, 12% O2) reduces both the partial pressure of O2 (PO2) and the O2 bound to hemoglobin [HbO2], we utilized carbon monoxide (CO) as a tool by which to reduce HbO2 independently of PO2, thereby determining the relative contributions of each in the regulation of VEGF in man. METHODS: At rest subjects breathed either normoxia (N), H, or hyperoxia (O2 = 85%) with a 20% HbCO load (CO+Hyper) for one hour. To complement prior data revealing no augmentation of the VEGF exercise signal with the addition of H, subjects performed single leg knee-extensor exercise (KE) in CO+Hyper. RESULTS: Quantitative RT-PCR analysis of quadriceps muscle biopsy samples revealed no difference in VEGF mRNA gene expression at rest between normoxia (2.1 ± 0.6) and H (1.1 ± 0.3) or between normoxia (2.3 ± 1.3) and CO+Hyper (2.5 ± 0.7). Finally, the combined stimulus of CO+hyper (0.6 ± 0.2) with KE also failed to reveal a difference in VEGF mRNA levels when compared to the normoxic exercise bout. CONCLUSION: With the links between O2 availability, exercise and angiogenesis, these findings reveal a surprising insensitivity of human VEGF mRNA to both PO2 and HbO2 at rest and during exercise. Supported by NIH grant HL 17731.