Oxidative stress due to hypoxia/reoxygenation induces angiogenic factor VEGF in adult rat myocardium: possible role of NFkappaB.

INTRODUCTION: Oxidative stress, as exerted by free radicals within biological systems, is known to exert numerous physiological and pathological effects on the cardiovascular system. Short-term exposure to environmental conditions such as low oxygen tension can cause such oxidative stress in vivo through inhalational hypoxia/reoxygenation. In this report the effects of different durations of hypoxia were investigated on myocardial protein expression of vascular endothelial growth factor (VEGF). a major angiogenic growth factor, and also explore the possible modulatory role of transcription factor NFkappaB on such expression.
METHODS: Forty eight male Sprague-Dawley rats (300 g b.w.) were randomly divided into four groups and subjected to either 1, 2 or 4 h of systemic normobaric hypoxemic hypoxia (10+/-0.4% O2) in an anesthesia chamber, or to 4 h of normoxia (ambient 20.9+/-0.4% O2) to time-match the maximal hypoxic duration. All rats were then kept under normoxic conditions. Rats were sacrificed and hearts harvested either after 2 h for later electrophoretic mobility gel shift assay for NFkappaB, or after 24 h for later Western blot analysis for VEGF.
RESULTS: Western blot analysis for VEGF revealed significantly elevated protein expression (2.4-fold compared to baseline control) in the I h group. This elevated level persisted in the 2 and 4 h groups as well. Two hours post-hypoxia gel shift assay for NFkappaB indicated significant nuclear translocation and DNA binding of this transcription factor in the 1 and 2 h groups, with moderate decrease in the 4 h group.
CONCLUSION: In vivo oxidative stress caused by systemic inhalational hypoxemic hypoxia increases cardiac VEGF protein expression and may trigger myocardial angiogenesis. The results suggest that NFkappaB modulates such an effect.