Oxidative stress due to hypoxia/reoxygenation induces angiogenic factor VEGF in adult rat myocardium: possible role of NF kappa B

Introduction: Oxidative stress, as exerted by free radicals within biologic al systems, is known to exert numerous physiological and pathological effec ts on the cardiovascular system. Short-term exposure to environmental condi tions such as low oxygen tension can cause such oxidative stress in vivo th rough inhalational hypoxia/reoxygenation. In this report the effects of dif ferent durations of hypoxia were investigated on myocardial protein express ion of vascular endothelial growth factor (VEGF), a major angiogenic growth factor, and also explore the possible modulatory role of transcription fac tor NF kappaB on such expression. Methods: Forty eight male Sprague-Dawley rats (300 g b.w.) were randomly divided into four groups and subjected to e ither 1, 2 or 4 h of systemic normobaric hypoxemic hypoxia (10 +/- 0.4% O-2 ) in an anesthesia chamber, or to 4 h of normoxia (ambient 20.9 +/- 0.49/0 O-2) to time-match the maximal hypoxic duration. All rats were then kept un der normoxic conditions. Rats were sacrificed and hearts harvested either a fter 2 h for later electrophoretic mobility gel shift assay for NF kappaB, or after 24 h for later Western blot analysis for VEGF. Results: Western bl ot analysis for VEGF revealed significantly elevated protein expression (2. 4-fold compared to baseline control) in the 1 h group. This elevated level persisted in the 2 and 4 h groups as well. Two hours post-hypoxia gel shift assay for NF kappaB indicated significant nuclear translocation and DNA bi nding of this transcription factor in the 1 and 2 h groups, with moderate d ecrease in the 4 h group. Conclusion: In vivo oxidative stress caused by sy stemic inhalational hypoxemic hypoxia increases cardiac VEGF protein expres sion and may trigger myocardial angiogenesis. The results suggest that NF k appaB modulates such an effect. (C) 2000 Published by Elsevier Science irel and Ltd. All rights reserved.