부산대학교 도서관

Reactive oxygen species (ROS) have been shown to play a role in promoting angiogenesis. We have developed a mouse model where left pulmonary artery ligation (LPAL) consistently induces the formation of a new systemic vasculature to the ischemic lung. To investigate whether ROS play a role in angiogenesis in our model, we assessed the effects of ROS down-regulation by pre-treating mice with N-acetylcysteine (NAC) (n=7). We also assessed the effects of ROS upregulation using mice deficient in the antioxidant promoting transcription factor Nrf2 (n=8) on new vessel growth. Pretreatment of C57Bl/6J mice with intraperitoneal NAC (5mg/10g body weight) at 24, 12 and 0 hours prior to LPAL and orally for 14 days afterwards resulted in a decrease in systemic blood flow to the left lung as assessed by radiolabeled microspheres compared to vehicle treated controls (54% control; p<0.002). Furthermore, Nrf2-deficient mice (CD-1) 14 days after LPAL demonstrated a significant increase in blood flow relative to wild type CD-1 LPAL mice (200% control; p<0.02). These data collectively suggest that ROS are involved in promoting systemic angiogenesis in response to chronic non-hypoxic ischemia in the mouse lung. NHLBI, HL71605 [ABSTRACT FROM AUTHOR]